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Although the coexistence of Crohn’s disease (CD) and pemphigus has been reported in several individuals, the association between the two conditions was not investigated systematically in the past. A recent association between pemphigus and ulcerative colitis has been reported. The study aims to estimate the association between pemphigus and CD using a large-scale real-life computerized database.A cross-sectional study was carried out comparing pemphigus patients with age-matched, sex-matched, and ethnicity-matched control participants in terms of the prevalence of CD. χ2-Test and t-test were used for univariate analysis and a logistic regression model was used for multivariate analysis. The study was carried out utilizing the computerized database of Clalit Health Services ensuring 4.5 million patients.A total of 1985 pemphigus patients and 9874 controls were included in the study. The prevalence of CD was comparable in patients with pemphigus and controls [0.4 vs. 0.3%, respectively; odds ratio (OR): 1.2; 95% confidence interval (CI): 0.5–2.5; P=0.688]. In an age-stratified analysis, a significant association was observed between pemphigus and CD in patients younger than 40 years (2.1 vs. 0.4%, respectively; OR: 5.1; 95% CI: 1.0–25.7; P=0.027). In a multivariate analysis adjusting for potential confounding factors, no independent association between the two conditions was found (OR: 0.9; 95% CI: 0.4–2.0; P=0.828). Study findings were robust to sensitivity analysis that included patients under pemphigus-specific treatments.Unlike ulcerative colitis, CD was not associated with pemphigus. Further research is warranted to understand the pathophysiology of these observations better.