Objective: To assess the efficacy of monoclonal anti-tumor necrosis factor (TNF)-α agents in patients with anterior uveitis (AU) in terms of decrease of recurrences, variation of visual acuity and steroid sparing effect and to identify any demographic, clinical or therapeutic variables associated with a sustained response to monoclonal TNF-α inhibitors. Methods: Data from patients suffering from AU treated with adalimumab, infliximab, golimumab or certolizumab pegol were retrospectively collected and statistically analyzed. Results: Sixty-nine patients (22 males, 47 females), corresponding to 101 eyes, were enrolled. The mean follow-up period was 29.25±23.51 months. The rate of ocular flares decreased from 42.03 events/100 patients/year recorded during the 12 months preceding the start of TNF-α inhibitors to 2.9 flares/100 patients/year after the start of treatment (p<0.0001). The overall decrease in ocular flares was 93.1%. No statistically significant changes were identified in the best corrected visual acuity during the follow-up period (p>0.99). The number of patients treated with corticosteroids at baseline was significantly higher compared with that referred to the 12-month evaluation (p<0.001) and to the last follow-up visit (p=0.006). Concomitant treatment with conventional disease modifying anti-rheumatic drugs (cDMARDs) represented the sole clinical, demographic or therapeutic variable associated with long-term treatment duration (p=0.045, R2=0.87). Conclusions: Monoclonal TNF-α inhibitors induce a remarkable decrease in the recurrence of AU during a long-term follow-up period and lead to a significant steroid sparing effect along with stabilization of visual acuity. Concomitant treatment with cDMARDs represented the sole variable associated with treatment duration in the long-term.