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Among the immune-mediated reactions, anaphylaxis is the most severe form. As a postoperative analgesia, diclofenac sodium, and nonsteroidal anti-inflammatory drug is commonly used. Intravenous (IV) diclofenac sodium-induced anaphylaxis is very rare. We are presenting a case of IV diclofenac-induced anaphylactic reaction, occurred during the surgery in a female patient of 21 years of age. The sign and symptoms of the reaction resembled an anaphylactic reaction. Temporal relationship with IV diclofenac administration and development of the clinical features of the reaction found to be probable. The health-care professionals should be aware of such rare and serious reactions so that it can be diagnosed and treated early. The clinical importance associated with the case encouraged us to report this rare complication of IV diclofenac.