Background. Drug persistence is a crucial aspect of treatment success in psoriasis. Objectives. To record real-world evidence concerning drug survival of biologic agents used for psoriasis treatment and to detect associated modifying factors in Greece. Methods. This was a retrospective cohort study based on data extracted from the nationwide Greek prescription system. Included patients had psoriasis, with or without concomitant psoriatic arthritis (PsA), and had initiated biologics between 1 January 2016 and 31 December 2020. Results. We included 8819 patients who received 13 359 treatment lines. Among them, 76.8% of patients were biologic naive and 16.5% were diagnosed with concomitant PsA. The overall median drug survival was 34.3 months [95% confidence interval (CI) 32.6–36.5]. Drug persistence at 12, 24, 36 and 48 months of follow-up was 71.9%, 57.7%, 49.0% and 43.7%, respectively. Patients receiving brodalumab had the highest drug survival rate in the first 2 years, while secukinumab had the highest rates beyond this period. Overall, drug survival rates were higher in the first treatment line (median 51.1 months, 95% CI 47.1 to not reached) than in the second line and onwards (median 21.7 months, 95% CI 20.0–23.5). Treatment line, PsA status, age and sex were found to significantly affect drug survival rates. Conclusions. Our findings confirm previous reports regarding the importance of efficient first-line biologics and the vulnerability of patients to coexistent PsA. The use of antibodies against interleukins confers high drug survival rates. These results will assist clinical management of patients with psoriasis in Greece.