We assessed the effect of smoking on the clinical course of ulcerative colitis in 209 subjects by comparing disease severity in smokers and non-smokers as measured by yearly number of hospitalizations for ulcerative colitis treatment and the need for a colectomy. Hospitalization for ulcerative colitis treatment occurred less frequently in persons who smoked after disease onset, but the colectomy rate in persons who smoked after disease onset and non-smokers was similar. Both hospitalization and colectomy for treatment of ulcerative colitis occurred more frequently among smokers who quit before disease onset. Furthermore, hospitalization and colectomy occurred most frequently in the heaviest smokers who quit before disease onset. We found no strong evidence of a therapeutic effect of smoking after ulcerative colitis onset on this illness's clinical course, but smoking before disease onset may affect the clinical severity of this illness.