INTRODUCTION Treatment of nail psoriasis can be challenging and unsatisfactory. The aim of this study was to compare the efficacy of three different anti-TNF-α agents on nail psoriasis in patients affected by psoriasis. MATERIALS AND METHODS Seventy-two patients with nail psoriasis were evaluated in this open, 24 weeks, prospective study. Patients were enrolled in three groups of treatment: adalimumab, etanercept or infliximab. Severity of nail psoriasis was assessed by the Nail Psoriasis Severity Index (NAPSI) at baseline, week 14, and 24. RESULTS Sixty patients were included in the study. The mean NAPSI was 33.77. In the adalimumab group, the mean NAPSI score was 33.1 (± 14.9) at baseline, 21 (± 8.91) at week 14 and 11.4 (± 4.6) at week 24 (p < 0.0002). In the etanercept group, the mean NAPSI was 34.8 (± 12.38) at baseline, 23.6 (± 10.43) at week 14, and 10.6 (± 5.25) at week 24 (p < 0.0016). In the infliximab group, the mean NAPSI was 33.3 (± 9.76) at baseline, 14.9 (± 4.20) at week 14 (p < 0.001) and 3.1 (± 3.27) at week 24 (p < 0.00001). At week 14 efficacy was higher in infliximab group compared to adalimumab and etanercept groups (p < 0.05). CONCLUSIONS Among the three agents, in the infliximab group a significant improvement in nail psoriasis was observed as early as week 14 of therapy whereas in the adalimumab and etanercept groups at week 24.