The efficacy and safety of acitretin was evaluated retrospectively in a cohort of 46 patients with moderate to severe plaque psoriasis (Psoriasis Area and Severity Index (PASI) range 10-42). Patients were treated at an initial dose of 10 mg/day acitretin, which was then gradually increased until the best therapeutic effect with the fewest adverse effects was reached (< 50 mg/day) and later decreased and maintained at the lowest effective dosage. Efficacy measures were: (i) PASI75 (75% improvement) and PASI50 between 10 and 16 weeks; and (ii) PASI75 even after 16 weeks of treatment. At weeks 10-16, PASI75 and PASI50 were achieved by 47.8% and 87% of the patients, respectively. Overall, 67.3% reached PASI75. Adverse events occurred in 18 patients (39.1%); among these, 4 (8.7%) discontinued acitretin. Our findings suggest that acitretin at an initial low, gradually escalating dose, and subsequently maintained at the minimal effective dose, is a suitable treatment option for plaque psoriasis as it provides clear-cut improvement in most treated patients while minimizing the risks of side-effects.