AIM:To investigate whether semi-vegetarian diet (SVD) has a preventive effect against relapse of Crohn's disease (CD) in patients who have achieved remission, who are a high-risk group for relapse. METHODS:A prospective, single center, 2-year clinical trial was conducted. Twenty-two adult CD patients who achieved clinical remission either medically (n = 17) or surgically (n = 5) and consumed an SVD during hospitalization were advised to continue with an SVD and avoid known high-risk foods for inflammatory bowel disease. The primary endpoint was clinical relapse defined as the appearance of active symptoms of CD. Kaplan-Meier survival analysis was used to calculate the cumulative proportion of patients who had a relapse. A 2-year analysis of relapse rates of patients who followed an SVD and those who did not (an omnivorous diet group) was undertaken. RESULTS:SVD was continued by 16 patients (compliance 73%). Remission was maintained in 15 of 16 patients (94%) in the SVD group vs two of six (33%) in the omnivorous group. Remission rate with SVD was 100% at 1 year and 92% at 2 years. SVD showed significant prevention in the time to relapse compared to that in the omnivorous group (P = 0.0003, log rank test). The concentration of C-reactive protein was normal at the final visit in more than half of the patients in remission who were taking an SVD, who maintained remission during the study (9/15; 60%), who terminated follow-up (8/12; 67%), and who completed 2 years follow-up (7/10; 70%). There was no untoward effect of SVD CONCLUSION:SVD was highly effective in preventing relapse in CD.