BACKGROUND: Many patients report questionable drug hypersensitivity reactions (DHR) to betalactams. Allergological evaluation is required for objectivation. Recently, some researchers advocated direct drug provocation tests (DPTs) omitting a prior allergy-workup. However, DPTs bare the risk of severe side effects and are a scarce resource in overloaded healthcare-systems. We investigated the value of an approach using only the broadly available methods drug-specific history, specific IgE, and skin tests without DPT. METHODS: We conducted a chart review in a retrospective cohort of 932 patients in an allergy outpatient centre from 2016-2017. Patients had been submitted to drug-specific history and specific IgE-, skin prick-, intradermal- and patch-tests with early and late readings with a series of penicillins and cephalosporins but DPTs were no option. RESULTS: Overall, positive in vitro and/or skin tests were found in 96/932 (10.3%) patients. Drug-specific IgE was detected in 40/932 (4.3%) patients, 61/787 (7.8%) patients had positive skin tests. In vitro tests to Pencillin V showed the highest rate of positivity 24/479 (5.0%) and early readings of ampicillin the highest amongst the skin tests 3/49 (6.1%). Immediate skin tests were more often positive than delayed ones (75:45). The combination of all parameters including drug-specific history solved 346/932 (37.1%) cases while 586/932 (62.9%) remained unresolved. Females and younger children carried a lower risk for positive tests (p<0.05, Χ²-test). CONCLUSIONS: Testing with betalactams applying simple, cheap, and safe skin and blood tests can solve a third of DHR-cases on a high throughput scale.