The German (PsoBest) and Swiss (SDNTT) Psoriasis Registries collect data on the efficacy of anti-psoriatic treatments among smokers and non-smokers. Out of 5,346 patients included in these registries, 1,264 met the inclusion criteria for this study. In the smoking group, 715 (60.6%) reached therapy response at month 3, compared with 358 (63.7%) in the non-smoking group. At month 6, 659 (74.1%) vs. 330 (77%), and at month 12, 504 (76.6%) vs. 272 (79.0%) reached therapy response. Therefore, these data do not show that smoking affects the response rate of anti-psoriatic therapy after 3, 6 and 12 months. Psoriasis can involve the skin, joints, nails and cardiovascular system and result in a significant impairment in quality of life. Studies have shown a lower response rate to systemic anti-sporiatic therapies in smokers, and smoking is a trigger factor for psoriasis. The aim of this study was therefore to analyse the response to systemic therapies for psoriasis, with a focus on smoking. Prospectively collected data from patients with moderate to severe psoriasis included in the national psoriasis registries for Germany and Switzerland (Pso-Best and SDNTT) were analysed. Therapy response was defined as reaching a Psoriasis Area and Severity Index (PASI) reduction of 75%, PASI ≤ 3 or Dermatology Life Quality Index (DLQI) ≤ 1. Out of 5,346 patients included in these registries, 1,264 met the inclusion criteria for this study. In the smoking group, 715 (60.6%) reached therapy response at month 3, compared with 358 (63.7%) in the non-smoking group (p ≤ 0.269), 659 (74.1%) vs. 330 (77%) reached therapy response at month 6 (p ≤ 0.097), and 504 (76.6%) vs. 272 (79.0%) at month 12 (p ≤ 0.611). Therefore, these data do not show that smoking affects the response rate of anti-psoriatic therapy after 3, 6 and 12 months.