Objective: Our aim was to assess the role of the body mass index (BMI) in the clinical response to systemic treatment for psoriasis. Methods: A nationwide cohort study of patients receiving a new systemic treatment for plaque psoriasis at reference centres in Italy was conducted. Information was gathered through a web-based electronic form. Patients being maintained on the same medication and with data available at 8 and 16 weeks by March 31, 2007, were eligible. The outcome was a reduction in the Psoriasis Area Severity Index (PASI) of at least 75% at follow-up compared to baseline (PASI-75). Results: Out of 8,072 patients enrolled, 2,368 were eligible and analysable at 8 weeks and 2,042 at 16 weeks. PASI-75 was achieved by 819 patients (34.5%) at 8 weeks and 1,034 (50.6%) at 16 weeks. The proportion steadily decreased with increased values of BMI. Compared to normal weight (BMI = 20–24) the adjusted odds ratio for achieving PASI-75 in obese patients was 0.73 (95% CI = 0.58–0.93) at 8 weeks and 0.62 (95% CI = 0.49–0.79) at 16 weeks. The impact of the BMI did not show remarkable variations according to the drug prescribed at entry. Conclusion: The BMI affects the early clinical response to systemic treatment for psoriasis.