INTRODUCTION: There is paucity of data on the incidence of severe thiopurine (TP)-induced myelosuppression (TIM) among patients with inflammatory bowel disease (IBD). METHODS: Using the Veterans Affairs Healthcare System, we identified patients with IBD with normal pretreatment TP S-methyltransferase levels who received TPs for 6 months and developed severe TIM. RESULTS: Among 73,392 patients with IBD, 14,760 had received TPs, and 2,823 had a normal TP S-methyltransferase level. The incidence rate of severe TIM was 1.25 per 1,000 patient-years. DISCUSSION: The incidence of severe TIM was very low, calling into question the necessity of frequent long-term complete blood count monitoring among patients with IBD on TPs.