In 1840, Griffin was appointed assistant surgeon in the Army and served under General William J. Worth in Florida and, with the rank of captain, on the Southwest frontier at Fort Gibson, Griffin came to California for the first time with General Kearney on the trek from New Mexico in 1846. He was stationed in San Diego and in Los Angeles in charge of the military hospitals, visited the California Gold Country during the 1849 Gold Rush and was stationed in Benicia until 1852. In that period he was given duty in an expedition against the Yuma Indians on the Colorado River. He was assigned to Washington, D.C., in 1853 and resigned from the service in 1854.