Background: Drug hypersensitivity reactions (DHRs) are among the most frequent reasons for consultation in allergy departments and are becoming more common due to increasing prevalence and case complexity.Objective: To describe the most common drugs associated with clinical reactions, diagnostic methods used, and outcomes of allergic evaluations of a national drug allergy registry over a 12-year period were used.Methods: An observational, prospective, patient’s data registry-based study was conducted to analyze all referrals to the drug allergy outpatient clinics at Al-Rashed Allergy Center, Kuwait, between 2007 and 2019. Demographics, description of DHRs, and results of allergy tests to potential causative medications were reviewed. Diagnostic methods were focused mainly on skin tests (STs) and drug provocation test (DPT), when indicated.Results: We evaluated 1,553 patients with reported DHRs. The mean age of the population was 41.52 ± 16.93 years, and the study population consisted of 63.7% female patients. Hypersensitivity was finally confirmed in 645 (41.5%) of patients, probable in 199 (12.8%), and not confirmed/nonallergic in 709 (45.6%) patients. Anti-inflammatory drugs and analgesics contributed to 39.22% of all confirmed drug allergies, followed by antibiotics 38.1% (β-lactam antibiotics (BLs) constituted 73.98% of all antibiotics and 28.21% of all drugs), anesthetics 1.8%, and radio-contrast media 0.31%. The majority of reactions were non-immediate 51.44%. The most commonly presenting symptoms among confirmed patients were urticaria 57.80%, angioedema 42.50%, respiratory symptoms 47.60%, and erythema 33.60%. Symptoms of anaphylaxis/anaphylactic shock were reported by 284 patients (44.00%) among confirmed cases. The most common method of diagnosis was a positive clinical history (54.4% in BLs and 90.45% in nonsteroidal anti-inflammatory drugs (NSAIDs). Among confirmed allergy to BLs, a positive ST was obtained in 31.9% of patients and positive DPT in 13.7%.Conclusion: NSAIDs and antibiotics, mainly BLs, are the most commonly implicated in confirmed allergy. In both confirmed and not confirmed/nonallergic cases, BLs are the most frequently involved DHRs which are mainly immediate, and the most commonly presenting symptoms were urticaria, angioedema, and respiratory symptoms. Diagnosis was confirmed mainly by a positive clinical history and when indicated, by positive STs or a DPT.