Background/Objective: The purpose of our study was to provide evidence on the treatment choices, reasons, and results of switching between biologic agents in treating patients with psoriasis. Methods: We conducted a retrospective database search of six tertiary referral centers for pso-riasis patients between January 2007 and May 2019. We analyzed patient and treatment characteristics of all patients in the registry. Results: We enrolled 427 psoriatic patients treated with biologics, and 145 (34%) required a switch to another biologic. The reasons for discontinuing the first biologic agent were inefficacy (n = 106, 62.4%), adverse events (n = 28, 16.5%), and others (n = 36, 21.2%). At week 12, there was a 67.7% reduction in the Psoriasis Area and Severity Index (PASI) score of patients treated with their first biologic, and 51.4% reduction for the second. A drug survival analysis showed no statistically significant difference between the drug survival of first-line biologic agents, but ustekinumab had the highest survival rate among second-line biologics (log-rank p = 0.010). Multivariate analyses for overall drug discontinuation showed that the occurrence of psoriatic arthritis (OR: 1.883, 95% CI: 1.274–2.782, p = 0.001), nail involvement (OR: 2.334, 95% CI: 1.534–3.552, p < 0.001), and use of concomitant treatment (OR: 2.303, 95% CI: 1.403 –3.780, p = 0.001) are predictors for discontinuation. Conclusion: Discontinuation of treatment was most commonly due to inefficacy. Patients who switched to a different biologic agent showed a similar improvement in PASI scores compared to biologic-naive patients. Switching to a second biologic therapy due to inefficacy or adverse events caused by the first one may improve psoriasis.