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Studies have not established the optimal role for prophylaxis after surgery for Crohn's disease. Some suggest treatment should be initiated within the first month after surgery, whereas others advocate targeted treatment after endoscopic recurrence. In the present study, we compared the efficacy of these competing approaches.One hundred and ninety-nine Crohn's disease patients who underwent ileocecectomy between September 1993 and April 2008 were retrospectively divided into 3 groups based on treatment timing: immediate, tailored, and none. Groups were compared for differences in demographics, pathology, and surgical technique (Chi-square, ANOVA). Rate of symptomatic recurrence (Chi-square), and time to symptomatic recurrence were analyzed (log rank, multivariate Cox proportional hazards).Sixty-nine (34.7%) received immediate prophylaxis, 32 (16.1%) received tailored prophylaxis, and 98 (49.3%) did not receive any prophylaxis. The groups were similar, though patients receiving immediate prophylaxis were younger and less likely to be lost to follow-up. At 5 years, 62 (31.2%) patients had endoscopic, 46 (23.1%) had symptomatic, and 22 (11%) had surgical recurrences. On simple univariate analysis, patients treated in a tailored fashion at time of endoscopic recurrence appeared more likely than patients treated with immediate prophylaxis to have symptomatic recurrence (43.7% vs 28.9%; P = .02), However, when censored for length of follow-up on multivariate analysis, the only enduring predictor of symptomatic recurrence was Charlson Comorbidity Index (P = .048). Timing of treatment, medicine used for immunoprophylaxis, age, history of prior resection, presence of active disease, and type of anastomosis were not predictive of symptomatic recurrence.Patients offered prophylaxis tailored to endoscopic recurrence have a similar time to symptomatic recurrence as those offered prophylaxis immediately. This suggests that a tailored treatment within a strict protocol of preemptive endoscopic surveilance may be reasonable.