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Angioedema is a frequently reported side effect of angiotensin-converting enzyme inhibitors. The literature suggests that immunosuppressed transplant patients are at an increased risk for this adverse condition. A 62-year-old African American man presented with acute unilateral angioedema attributed to angiotensin-converting enzyme inhibitor initiation. A PubMed literature search regarding unilateral angioedema produced only 3 reported cases confirming an uncommon presentation of an otherwise common adverse drug event. The cases raised questions regarding evidence-based management of drug-induced angioedema, effectiveness of current medical management regimens and the potential of other treatment options. Our objective was to review the presentation, diagnosis and acute management of a common adverse drug effect based on an uncommon patient presentation.