Our bi‐specialty clinic was established to systematically investigate patients with suspected peri‐operative hypersensitivity reactions. Four hundred and ten patients were studied; 316 following an intra‐operative reaction (‘postoperative’ group) and 94 with a previous history of reaction, referred before undergoing anaesthesia (‘pre‐operative’ group). In the postoperative group, 173 (54.7%) were diagnosed with IgE‐mediated reactions: 65 (37.6%) to neuromuscular blocking drugs; 54 (31.2%) antibiotics; 15 (8.7%) chlorhexidine and 12 (6.9%) patent blue dye. Reactions were severe in 114 patients (65.9%). All reactions to patent blue dye were severe. We identified IgE sensitisation in 22 (13.2%) cases with isolated mucocutaneous reactions. Only 173 (54.7%) patients had serum tryptase samples taken. Referrers' suspected causal agent was confirmed in only 37.2% of patients. Of 94 patients reviewed ‘pre‐operatively’, 29 (30.8%) were diagnosed with IgE‐mediated hypersensitivity reactions, reinforcing the importance of investigating this group of patients. Knowledge of the range of causative agents identified in our study should guide the investigation of suspected peri‐operative hypersensitivity reactions.