Identification of the etiology of drug allergy is a crucial step in its management, and it depends mainly on the study of the patient’s history; this is because skin testing is not always reliable, and drug challenge tests are hazardous. Cellular antigen stimulation test (CAST) is a diagnostic tool that is used for the detection of sulfidoleukotrienes released by basophils stimulated by allergens in vitro. A case-control study was conducted to evaluate the efficacy of cellular antigen stimulation test in the diagnosis of patients with a history of allergy to drugs. The study included 90 patients, divided equally into 2 groups (45 in the drug allergic group, and 45 in the control group). Full allergy history was taken, skin prick test (SPT), and patch test for penicillin and non-steroidal anti-inflammatory drugs (NSAIDs) were done. Serum-specific IgE test and CAST by the enzyme-linked immunosorbent assay (ELISA) test were also performed. The specificity of CAST for drug allergy was 84.4% and the sensitivity was 48.9%. The specificities of SPT, patch test and specific IgE in the allergic group were 91.1%, 91.1% and 73.3%, while their sensitivities were 51.1%, 33.3%, and 62.2%, respectively. In spite of the sub-optimal sensitivity and high specificity of CAST test in the diagnosis of drug allergy, this test is an important diagnostic tool. It can be used especially in the cases with immune-mediated type of allergy, when other diagnostic tests are not dependable, or unavailable.