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Background/Aims: To evaluate the association of psoriasis with selected medical conditions and a number of drugs used before diagnosis. Methods: Multicenter case-control study involving outpatient services of 20 general and teaching hospitals. Entry criteria for cases were a first diagnosis of psoriasis made by a dermatologist and a history of skin manifestations of no more than 2 years after the reported onset of the disease. Controls were the first eligible dermatological patients observed on randomly selected days in the same centers as cases. A total of 560 cases and 690 controls were recruited. Results: The odds ratio (OR) of psoriasis was 0.8 (95% confidence interval, CI, 0.5–1.3) in hypertensive subjects, 1.1 (95% CI 0.6–2.0) in diabetics and 1.1 (95% CI 0.7–1.7) in hyperlipidemic subjects. Histamine 2 receptor antagonist exposure was negatively associated with psoriasis: OR 0.3 (95% CI 0.1–0.8). Conclusion: Our study rules out a strong association of psoriasis at its first ever diagnosis with common chronic conditions. The reported associations of psoriasis with relatively common conditions such as diabetes mellitus, hypertension and hyperlipidemia may represent a late effect of well-known risk factors for psoriasis such as smoking and overweight or reflect factors related to the long course of psoriasis itself.