Background/Objectives: Despite substantial progress in the management of psoriasis, evidence on as-needed dosing strategies for biologic therapies remains scarce. In this context, the present study aimed to assess the effectiveness of a previously defined as-needed bimekizumab (BKZ) dosing regimen in a larger cohort of patients with psoriasis, as well as to identify clinical factors associated with treatment response. Methods: In this retrospective study, medical records of 64 patients with moderate-to-severe psoriasis treated with BKZ between May 2023 and November 2025 at a specialized psoriasis unit in Madrid, Spain, were reviewed. Patients followed an off-label, as-needed dosing regimen, consisting of two initial 320 mg doses at Weeks 0 and 4, with subsequent administrations only upon loss of a PASI 90 response. The primary outcome was the proportion of patients achieving and maintaining optimal disease control (PASI 90) over time. The duration of treatment effect was defined as the interval between the second dose and loss of PASI90 in the absence of further treatment. Safety outcomes were also evaluated. Results: A total of 59 out of 64 patients achieved a PASI 90 response after the initial two BKZ doses, and all maintained disease control with the as-needed dosing strategy over time. On average, patients received approximately one-third of the doses expected under the standard dosing regimen. The mean duration of treatment effect following the second dose was approximately 24 weeks. Systemic and bio-naïve patients presented the longest treatment effect duration under the as-needed dosing regimen. Oral candidiasis was reported in two patients and resolved without complications. Conclusions: This study reinforces previous evidence supporting the effectiveness of an as-needed BKZ dosing strategy, particularly in patients naïve to systemic and biologic therapies for psoriasis. Nevertheless, larger prospective studies are required to confirm these findings.