Tripler was regularly transferred over the whole country before he served in the Second Seminole War and the Mexican–American War. During the Mexico City Campaign he was assigned as Medical Director of General David E. Twiggs regular division and was afterwards ordered to organize and command the army's general hospital in the city. After the war he continued his service in New York, Michigan, Kentucky and California. In 1852 Tripler was part of an expedition tasked with traveling down the east coast from New York to Panama where they would march across the country to the west coast and sail back. During the march through Panama, the unit's soldiers began to have an outbreak of cholera, malaria, diarrhoea, and dysentery which enlightened Tripler to the inadequate medical procedures in place by the Army. After the eruption of the Civil War Tripler was ordered to Washington, and on August 12, 1861, he was appointed Medical Director of the Army of the Potomac. Participating in the Peninsula Campaign of 1862 he was, under pressure from the United States Sanitary Commission, replaced by Jonathan Letterman. He was allowed to choose his next appointment, and accordingly became Chief Surgeon of the Department of the Lakes. Tripler stayed on this position during the war, and was appointed Brevet Brigadier General on March 13, 1865. Diagnosed with a malignant tumor of the glands of the neck in early 1866 he died on October 20, 1866.