Intake of drugs is considered a risk factor for psoriasis. The aim of this study was to investigate the association between drugs and psoriasis. A case-control study including 110 patients who were hospitalized for extensive psoriasis was performed. A control group (n = 515) was defined as patients who had undergone elective surgery. A case-crossover study included 98 patients with psoriasis. Exposure to drugs was assessed during a hazard period (3 months before hospitalization) and compared to a control period in the patient's past. Data on drug sales were extracted by data mining techniques. Multivariate analyses were performed by logistic regression and conditional logistic regression. In the case-control study, psoriasis was associated with benzodiazepines (OR 6.9), organic nitrates (OR 5.0), angiotensin-converting enzyme (ACE) inhibitors (OR 4.0) and non-steroidal anti-inflammatory drugs (NSAIDs) (OR 3.7). In the case-crossover study, psoriasis was associated with ACE inhibitors (OR 9.9), beta-blockers (OR 9.9), dipyrone (OR 4.9) and NSAIDs (OR 2.1). Extensive psoriasis may be associated with intake of ACE inhibitors, NSAIDs or beta-blockers.