We report a case of immediate severe anaphylaxis to hydroxypropyl methylcellulose (HPMC) on 2 separate occasions during cataract surgery in a 71-year-old patient. Skin prick tests were positive for HPMC, a constituent of Ocucoat and Xylocaine gel, which were administered intraocularly during surgery. Skin prick tests were also positive for methylcellulose. Based on symptoms and clinical signs of anaphylaxis following 2 separate cataract operations together with positive prick tests to HPMC, HPMC is the most plausible cause of the reactions. The patient has since had uneventful surgery for a detached retina avoiding HPMC. This case stresses the importance of considering all medication given to patients as possible causes of an anaphylactic reaction.