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Acute pancreatitis (AP) is a common inflammatory condition of the pancreas, often caused by gallstones or alcohol. However, drug-induced acute pancreatitis (DIAP) is a rare and challenging diagnosis that requires thorough medication reconciliation and a high degree of clinical suspicion. This case report describes a 58-year-old African-American female patient who presented to the emergency department on two occasions with severe epigastric pain, elevated lipase levels, and imaging findings consistent with AP. After excluding common causes of AP, hydrochlorothiazide (HCTZ) was identified as the likely trigger. Discontinuation of HCTZ resulted in symptom resolution, with no recurrence during follow-up. This case underscores the importance of considering DIAP, particularly in patients on HCTZ who present with unexplained, recurrent AP., Competing Interests: Human subjects: Consent for treatment and open access publication was obtained or waived by all participants in this study. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2025, Linkous et al.)