Objectives: The aim of this study was to analyze the processes and outcomes of tramadol hypersensitivity testing at the Outpatient Clinic for Clinical Pharmacology of the Clinical hospital Center KBC Osijek, to evaluate the reliability of the skin test in relation to the findings of a subsequent test with oral drug exposure and to examine the connection between the test results and the type and severity of the previous reaction, comorbidities, age and gender. Study design: Cross-sectional study with historical data. Subjects and methods: The research included patients tested for hypersensitivity to tramadol in the Outpatient Clinic of the Diagnostic and Therapeutic Department of Clinical Pharmacology of the Clinical hospital Center KBC Osijek, in the period from January 1st 2019, until December 31st 2023. On the base of the subjects’ medical records, demographic data and data on previous adverse reactions to tramadol and other drugs, comorbidities and hypersensitivity to other allergens were collected and they were analyzed in relation to the results of skin tests and tramadol provocation test. Results: The research included 27 subjects, 25 of whom were women (92.6%) and 2 were men (7.4%). The arithmetic mean of the average age of the subjects was 55.5 years. All the tests performed gave negative results in all subjects. The results of the skin tests completely coincided with the results of the tramadol provocation test. No correlation was found between the test results and the investigated variables. Conclusion: In this cross-sectional study, hypersensitivity to tramadol was not demonstrated in any subject by any of the skin tests. The complete concordance of skin tests with tramadol challenge tests was demonstrante in all patients, which is the proof of reliability of those tests in this sample of research subjects.