Background: There is a known female predominance in immunological conditions. Gender differences have also been demonstrated in perioperative hypersensitivity. The aim of this study was to investigate gender differences in the incidence of perioperative allergic reactions in Norway from 1997 to 2017. Methods: Spontaneous reports on allergic reactions during anesthesia were collected, and information about demographic, clinical and laboratory findings were recorded. Results: Women account for 66% of reported cases, and gender difference was most pronounced in fertile women (ages 14 to 51), where 74% of reports were from women. After withdrawal of the only pholcodine containing cough syrup on the market in 2007, the female predominance fell from 72 to 60% in all age groups. We found no differences in severity of the reaction or in laboratory findings between men and women. Conclusions: Women are at increased risk of suffering perioperative hypersensitivity reactions. The gender difference was less pronounced after the withdrawal of pholcodine.