Background: Acitretin has been linked to the development of psychiatric disturbance. Objectives: The aim of this study was to assess the psychiatric hazards in patients with psoriasis prescribed acitretin compared with those prescribed disease-modifying antirheumatic drugs (DMARDs). Methods: This is a nationwide matched cohort study. From Taiwan’s National Health Insurance Research Database, adult patients with psoriasis between 1997 and 2013 were screened. Patients prescribed acitretin for at least 30 days per year on average (acitretin cohort) were matched 1:2 with those prescribed DMARDs for at least 30 days per year on average (reference cohort), by means of age, gender, and psoriasis duration. Patients prescribed medication of the corresponding cohort for more than 7 days during the observation period were excluded. Cumulative incidences of psychiatric disorders in both cohorts were plotted with the Kaplan-Meier method. The modified Cox regression models were constructed to estimate hazard ratios (HRs). Results: In total, 1,152 and 2,304 patients in the acitretin and the reference cohorts, respectively, were included. The 4-year cumulative incidence of overall psychiatric disorders (19.62% vs. 12.06%; p < 0.001), mood disorders (12.81% vs. 7.67%; p < 0.001), and psychosis (7.21% vs. 4.63%; p < 0.001) in the acitretin cohort was significantly higher than that in the reference cohort. Acitretin was independently associated with psychiatric disorders (HR 1.51, 95% confidence interval [CI] 1.23–1.85). The risk is more accentuated in the subgroups of comorbid chronic liver disease (HR 2.60, 95% CI: 1.56–4.33) or psoriatic arthritis (HR 3.23, 95% CI: 1.75–5.97). Other independent risk factors included insomnia, acute coronary syndrome, females, and age. Conclusions: Compared with DMARDs, acitretin was associated with higher hazards of psychiatric disorders among psoriasis patients.