5-aminosalicylic acid has been reported to be able of inducing acute pancreatitis as an adverse reaction. However, in most case reports, rechallenge of the drug is missing; therefore, evidence is still needed to confirm its role in the clinical course of acute pancreatitis and its influence on the outcome. Here, we report a case of recurrent acute pancreatitis secondary to 5-aminosalicylic acid, with positive unintentional rechallenge. A systematic search of the literature was performed and 42 cases from 35 articles were summarized concerning the clinical course of 5-aminosalicylic acid induced acute pancreatitis.