Acute pancreatitis (AP) is an inflammatory disease associated with abdominal pain and elevated serum pancreatic enzymes. The most common etiologies are gallstones and alcoholism. Drug-induced AP is quite rare, lacks a solid understanding and has been occasionally reported. The diagnosis requires a great suspicion and a careful exclusion of other causes. We present a case of a 37-year-old man, previously diagnosed with leprosy that developed acute pancreatitis after starting the multibacillary polychemotherapy (PCT/MB). After a month of treatment and the discontinuation of the PCT/MB, the therapy was restarted and a new episode of AP occurred. Three months after this last episode, the PCT/MB was reintroduced, changing one of the medications and the patient had no recurrence of AP or other reactions. Therefore, it is important to take into account that there is a risk of acute pancreatitis in patients on multidrug therapy (MDT) for leprosy.