Angioedema with macroglossia is a rare complication of anesthesia. We present a clinical case of post-operative development of angioedema presenting as macroglossia in a patient receiving chronic therapy with lisinopril, who developed symptoms in the early post-operative period following surgery in a lateral position, when a laryngeal mask airway was used. Possible mechanisms of angioedema and macroglossia development in our patient are discussed along with potential underlying predisposing mechanisms and available therapeutic approaches.