The impact of thiopurines (TP) on the long-term outcome of early Crohn disease (CD) is still controversial. The present study designed as a comparison of conventional step-care to alternative treatment paradigms for disease progression.This longitudinal cohort study examined the established CD patients from a university-based inflammatory bowel disease referral center. Outcomes of mucosal healing (MH), CD-related surgery or hospitalization, and clinical remission were compared based on timing of initiation of TP therapy. The cumulative incidence of events was estimated by Kaplan-Meier method.One-hundred ninety patients with early CD were included. After a median follow-up of 57 months (interquartile range, 31.3-76.2), 29 patients undergone abdominal surgeries, 48 patients hospitalized, and 68 patients experienced clinical flares. A higher cumulative proportion of patients in the top-down (TD) group achieving MH than both the accelerated step-up (AC) group and conventional management (CM) group at month 36 (78.8% vs 39.9% and 42.2%, respectively; P = 0.001). There was a trend, albeit not significant, for an increased proportion of patients free of CD-related intestinal surgery in the TD group at month 60 (P = 0.16). However, among secondary outcomes, an early TP-based AC or TD strategy was not associated with improvement in clinical remission rates compared with a CM strategy at month 60 (P = 0.79). No significant difference was observed between early TP and CM for rates of MH, CD-related intestinal surgery or hospitalization, and clinical remission.Both AC and CM strategy were minimally effective for disease modification. TD strategy has the potential of achieving higher rates MH. Our results support the TD strategy in patients with early CD at risk for a disabling course.