Pierce engaged in the manufacture and sale of patent medicines and established the Invalids' Hotel and Surgical Institute.

His venture proved a success, with nearly one million bottles of Dr. Pierce's Smart Weed and other preparations shipped annually.

Pierce was elected as a Republican to the 46th United States Congress, holding office from March 4, 1879, to September 18, 1880, when he resigned.

After leaving Congress, Pierce resumed his business interests, and was publisher of a book, the People's Common-sense Medical Adviser.

Pierce died on February 4, 1914, at his home on St. Vincent Island, Florida, where he had founded a game preserve.