Background: Chlorhexidine is an antiseptic that may cause allergic contact dermatitis. Objectives: To describe the epidemiology of chlorhexidine allergy and characterize positive patch test reactions. Methods: This retrospective study analyzed patients patch tested to chlorhexidine digluconate 1% aqueous by the North American Contact Dermatitis Group, 2015-2020. Results: Of 14,731 patients tested to chlorhexidine digluconate, 107 (0.7%) had an allergic reaction; of these, 56 (52.3%) reactions were currently clinically relevant. Most (59%) reactions were mild (+), followed by strong (++, 18.7%) and very strong (+++, 6.5%). Common primary dermatitis anatomic sites in chlorhexidine-positive patients were hands (26.4%), face (24.5%), and scattered/generalized distribution (17.9%). Compared with negative patients, chlorhexidine-positive patients were significantly more likely to have dermatitis involving the trunk (11.3% vs 5.1%; P = 0.0036). The most commonly identified source category was skin/health care products (n = 41, 38.3%). Only 11 (10.3%) chlorhexidine reactions were occupationally related; of these, 81.8% were in health care workers. Conclusions: Chlorhexidine digluconate allergy is uncommon, but often clinically relevant. Involvement of the hands, face, and scattered generalized patterns was frequent. Occupationally related reactions were found predominantly in health care workers.