After studying in Paris (1856–61), Vedder returned to the United States at the outbreak of the Civil War. He supported himself by illustrating comic valentines and calisthenics books and by drawing for Vanity Fair. It was during this period of hardship that Vedder conceived such fantastic and melancholic works as “The Lair of the Sea Serpent” (1865) and “The Lost Mind” (1864–65). Vedder settled permanently in Rome in 1866 but made frequent trips to the United States. In 1884 he illustrated an edition of The Rubáiyát of Omar Khayyám, a work well suited to his imaginative style. He also executed a large lunette mural, “Rome,” for the Walker Gallery at Bowdoin College, Brunswick, Maine (1894), and five wall paintings and a mosaic for the Library of Congress (1896–97). His book Doubt and Other Things was published shortly before his death.