Background: Beta-lactam antibiotics are the most frequent drug family to cause allergic reactions. Herein, we examined the frequency of confirmed allergies to beta-lactam, as well as the sensitivity and negative predictive value (NPV) of skin testing in an adult population referred to a university allergy clinic in Switzerland. Methods: This is a retrospective analysis of the clinical records of patients who were investigated for a label of allergy to beta-lactam (penicillin, cephalosporin or carbapenem) between January 1 st 2011 and December 31 st 2018. Results: 582 patients were identified with a documented allergy to beta-lactam and 477 patients were systemically investigated by skin tests and/or drug challenge to confirm or rule out allergy. 262 patients reported a history of immediate reactions, 137 of delayed reactions, and 114 of unknown reactions. 88 (18.4%) patients had confirmed to any beta-lactam antibiotics; 64 (13.4%) with an immediate- and 24 (5%) with a delayed-type reaction. Most frequently identified allergy was penicillin (65 patients), followed by cephalosporin (21 patients) and carbapenem (2 patients). NPV of skin tests for all beta-lactam were 97.7% and 92.5% for immediate- and delayed-type reactions, respectively, and 96.3% and 92.1% when only penicillin was considered. Systemic allergic reaction occurred in 0.6% of skin tests and in 3.1% of drug challenges. Conclusions: Only 18% of patients with beta-lactam allergy label have a confirmed allergy and non-allergic patients can be safely delabelled through allergic workup based on skin tests and drug challenge. This approach supports the policy of saving second-line antibiotics through systemic allergy work-up.