Biologics are important treatment options for psoriasis; however, direct comparison of their efficacy, safety, and drug survival is insufficient in clinical practice. This retrospective single-center study aimed to compare the efficacy, safety, and drug survival of three commonly used psoriasis biologics (secukinumab, ustekinumab, and guselkumab) and identify the factors affecting drug survival in actual clinics in Korea. We enrolled 111 patients with moderate to severe psoriasis and for at least 56 weeks of follow-up; among these, 27, 23, and 61 were administered secukinumab, ustekinumab, and guselkumab, respectively. All groups were comparable with respect to their baseline characteristics. Secukinumab showed a rapid response, and guselkumab was superior in terms of a long-term response and complete remission compared with other biologics, while ustekinumab showed a lower efficacy compared with other biologics. All three biologics had a favorable and similar safety profile; however, allergic reactions and latent tuberculosis were more common with secukinumab and ustekinumab, respectively. Guselkumab was the most sustained biologic, and the survival rates of secukinumab and ustekinumab were similar. Drug survival was remarkably shorter in female patients and those with hypertension. Introduction of new biologics emerged as a negative factor for drug survival in clinical settings.