In the summer of 1828 Greene married Mary Elizabeth Vinton, sister of his best friend at West Point, David Vinton. Elizabeth gave birth to three children over the next four years: Mary Vinton, George Sears, and Francis Vinton Greene. While assigned to Fort Sullivan in Eastport, Maine, in 1833, tragedy struck Greene's family: Elizabeth and all three of their children died within seven months, probably from tuberculosis. To ease the pain on his mind and to escape the isolation and loneliness of peacetime Army garrison duty, he immersed himself in study of both the law and medicine, coming close to professional certification in both by the time he resigned his commission in 1836 to become a civil engineer.