Abstract: Omeprazole is a substituted benzimidazole that has gained widespread use in the treatment of acidic and peptic ulcer diseases. Though the adverse events with the drug are rare and involve mainly skin inflammation, urticaria, pruritus, alopecia and dry skin have been reported in 0.5-1.5% of patients. There are very few reports linked to angioedema and urticaria pertaining to Omeprazole or class of PPI as an adverse reaction. Hereby a case of 26-year-old male with hypersensitivity reaction characterized by angioedema (Swelling of lips and fore head). The patient develops adverse drug reaction to Omeprazole may become a hypersensitivity to whole class of PPIs; hence it is to be safer to consider the change of class of drugs for his future correspondence. Simultaneously, all the prescribers should be aware of this possible phenomenon of angioedema while prescribing omeprazole for different clinical indications.