BACKGROUND The coexistence of pemphigus and ulcerative colitis (UC) has been described, but the association between the two entities was not examined in the past. The primary endpoint of this study was to investigate the association between pemphigus and UC. MATERIALS AND METHODS Patients with pemphigus were compared to age-, sex- and ethnicity-matched control subjects regarding the prevalence of UC in a cross-sectional study. Chi-square and t-tests were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was conducted utilizing the computerized database of Clalit Health Services. RESULTS The study enrolled 1985 pemphigus patients and 9874 controls. The prevalence rate of UC was greater in patients with pemphigus than in controls (0.9% vs. 0.4%, respectively; p = .004). In a multivariate analysis pemphigus was independently associated with UC (odds ratio 1.9, 95% confidence interval 1.1-3.3, p = .034). This association was stronger among younger patients, and persisted after performing a sensitivity-analysis including only patients who were prescribed pemphigus-specific medications. CONCLUSIONS Pemphigus is significantly associated with UC. Thus, physicians treating patients with pemphigus should be aware of this possible association. Further research is warranted to better understand the mechanism underlying this association.