Many patients with chronic spontaneous urticaria (CSU) report various drugs as triggers of their symptoms and often avoid medication unnecessarily. Objective: To estimate the clinical impact of the drugs patients most frequently suspect of inducing CSU exacerbations.The prevalence of self-reported drug reactions was evaluated by questioning patients about their clinical history of urticaria and drug reactions and performing challenge tests with the suspect drugs. A group of healthy persons were included as controls to evaluate the prevalence of self-reported drug reactions.The study population comprised 245 patients with CSU and 127 healthy individuals. At least 1 adverse drug reaction was reported by 92 (37.5%) patients and 30 (23.6%) controls. Nonsteroidal anti-inflammatory drugs (NSAIDs) (27.7%) and ß-lactams (9.4%) were the most commonly reported drugs in the CSU group and the control group, respectively. Positive results in the challenge tests were less common than self-reports in the CSU group (13%) and the control group (0.7%).Self-reporting is generally not sufficient to confirm a drug reaction. Drug reactions to NSAIDs and ß-lactams are more frequent among patients who experience CSU than in those who do not. Drug challenge tests should be offered early during medical evaluation to avoid unnecessary restrictions.