Background: Although nail psoriasis occurs frequently in patients with psoriatic skin lesions, effective treatments are limited. Objective: Occurrence of nail psoriasis by type and incidence of nail clearance using the Nail Psoriasis Severity Index were evaluated. Methods: This was a 50-week, phase III study in which 378 patients with moderate to severe psoriasis were randomized 4:1 to infliximab (5 mg/kg) or placebo at weeks 0, 2, 6, and every 8 weeks through week 46, with placebo crossover to infliximab at week 24. Results: Of the 373 evaluated patients, 305 (81.8%) had baseline nail psoriasis. The right thumbnail was most often the worst involved nail, and pitting and onycholysis were the most common lesions. Among patients with baseline nail psoriasis, 6.9%, 26.2%, and 44.7% in the infliximab group had nail disease clearance at weeks 10, 24, and 50, respectively, versus 5.1% in the placebo group at week 24 (P <.001). Mean percent improvements in Nail Psoriasis Severity Index score at weeks 10 and 24 were 26.8% and 57.2%, respectively, in the infliximab group versus -7.7% and -4.1%, respectively, in the placebo group (both P <.001). At week 24, mean percent improvements in nail matrix and nail bed features were 52.9% and 69.2%, respectively (vs -1.9% and 18.4% for placebo; P <.001). Limitations: The study did not evaluate nail response beyond 1 year. Conclusions: Patients with psoriasis receiving infliximab experienced marked and sustained nail improvement. © 2008 American Academy of Dermatology, Inc.