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Objective The diagnostic work-up of a drug hypersensitivity reaction is indeed difficult. In general, medical documentation of allergic reactions in medical reports is usually highly deficient or non-existent. The aim of this study was to analyse the prevalence of self-reported drug allergies in the surgical population as well as the criteria used in the diagnosis of drug hypersensitivity reactions. Methods A prospective study with the consecutive participation of 1439 patients, following surgical intervention, attended the Post-Operative Care Unit. Previously, as a routine process during the pre-anesthesia consultation, all patients were questioned about whether they had any drug allergies to report and diagnostic work-up. Results The prevalence of self-reported drug allergies was 8.3% (119/1439): 3.6% considered themselves allergic to β-lactams and 2.4% to non-steroidal anti-inflammatory drugs. Approximately one-third of the subjects (40 out of the 119) had not been subjected to any allergy diagnostic procedure and with 79 (66.4%), the only diagnostic test used by the Allergy Unit had been the skin prick-test. None of those participating in the study had tryptase, methylhistamine, specific IgE or intradermal tests carried out to characterize the diagnosis of the allergic reaction. Conclusions These results show that self-reported drug allergies are highly prevalent and as yet little explored. It is an important prevalence which should bring about modifications to the prescription of certain medicaments. The medical personnel must be made aware of the need to make an accurate diagnosis of allergies to medicaments.