When Dr. Mudd returned home in March 1869, well-wishing friends and strangers, and inquiring newspaper reporters besieged him. Dr. Mudd was very reluctant to talk to the press because he felt they had misquoted him in the past. He gave one interview to a New York Herald reporter, but immediately regretted it. The reporter’s story contained several factual errors, and Dr. Mudd complained that it misrepresented his work at Fort Jefferson during the yellow fever epidemic. 

On the whole though, he must have been gratified to find that he continued to enjoy the respect and friendship of his friends and neighbors. Dr. Mudd resumed his medical practice, slowly brought the family farm back to productivity, and became active once again in the life of his community. In 1874, he was elected Master (chief officer) of the local farmers association, Bryantown Grange 47. In 1876, seven years after he returned home, he was elected Vice President of the local Democratic Tilden-Hendricks presidential election committee. Tilden lost that year to Republican Rutherford B. Hayes in a hotly disputed election. The next year Dr. Mudd ran as a Democratic candidate for the Maryland House of Delegates, but was defeated by the popular Republican William D. Mitchell.

Before he went to prison, Dr. and Mrs. Mudd had four children – Andrew, Lillian, Thomas, and Samuel. After prison, they had five more – Henry, Stella, Edward, Rose de Lima, and Mary Eleanor, known as ‘Nettie.’
 
Dr. Mudd’s 11 year-old daughter Stella was at her father’s bedside when he died on January 10, 1883. In a 1950 letter, an elderly Stella (Sister Rosamunda, Catholic nun) wrote to Dr. Richard D. Mudd, the son of Stella’s brother Thomas:

About a year before his death, he was not well and I was left to keep him company. While busy elsewhere he walked the floor. I thought he was saying ‘misery me’ - it was the Misererie. New Year’s Day he went to Mass, visited a very sick patient after Mass - had pneumonia - died Jan. 10th. The day before his death he said to my mother ‘Don’t wait till it is too late, send for the priest, I know I am going to die.’ The priest came, did not think need urgent and had to meet train, so did administer sacraments. The priest of Bryantown parish paid father a visit that day, heard his confession. Tom, your father, went for Father Southgate that night in snow and bitter cold. Father S. came, gave last rites - said prayers for dying and he was gone to God. I was present at death bed. Father said to my Mother - ‘It is not hard to die. I am just waiting for call of the Old Master.’ Mother said to him ‘How can you talk like that and leave me with a house full of children?’ He replied ‘God knows best’ (his last words) and died.

Dr. Mudd was just 49 years old when he died. He is buried in the cemetery at St. Mary’s Catholic Church in Bryantown, the same church where he first met John Wilkes Booth.

The Port Tobacco Times and Charles County Advertiser ran the following obituary for Dr. Mudd on January 19, 1883:

Death of Dr. Samuel A. Mudd

Dr. Samuel A. Mudd died at his residence near Bryantown in this county on Wednesday of last week after a short illness of pneumonia. So short had been his illness that no information of it had been received here, and being, as he was, in the prime of manly vigor, the sudden intelligence of his death received here on Friday was as great a surprise as it was an unfeigned and universal regret.

In the death of Dr. Mudd, Charles County has lost one of its most honored citizens, the profession a learned and useful member, while his family must endure the loss of a kind, loving and painstaking husband and father. He was ever ready to lend his aid and assistance to the poor and needy, and around the bed of pain and suffering his generous nature was ever ready to extend comfort and solace, with his means and the talents with which God had endowed him.

In the death of Dr. Mudd has passed from earth the last of those who were associated in the assassination of the lamented President Lincoln. As free from any guilty connection with conspirators in this crime, which will ever darken the pages of history, as an unborn babe, he nevertheless, upon bare suspicion was made to suffer from the brutal treatment of an enraged and ungovernable people. Awed by the circumstances of finding the assassin of the President in his house, he having imposed upon his generous nature by false statements as to the origin of his accident, his crime was simply not admitting the service rendered to Booth in setting his leg. Under the excitement prevailing at the time, Dr. Mudd denied any knowledge of Booth, or that he had been at his house. He was afraid to admit service rendered even under the misapprehension that the accident occurred by a fall from his horse while traveling through the county, as he had been told by Booth, would certainly secure his arrest and incarceration, his courage forsook him and he denied his having been with him, when upon search of his house the boot leg was found which had been cut from the broken limb with “J. Wilkes” written within it. To then tell the whole truth availed him nothing. He was tried for conspiracy in the assassination, convicted and sentenced to the Dry Tortugas for life, when after some three years he was pardoned by President Johnson. It is an injustice to the memory of a generous, warmhearted man to associate him with the guilty Booth. His only crime being rendering medical aid to Booth in his suffering, he not knowing Booth to be guilty of any crime, but laboring under the false impression he had sustained his accident in an innocent fall from his horse.

He was in his 48th year at the time of his death. He leaves a widow and six children to mourn his great loss.