The efficacy of biological treatment for severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) has recently been demonstrated through double-blinded clinical trials. The aim of this study was to provide preliminary real-world experience regarding biological therapy for uncontrolled CRSwNP. The records of patients who received biological treatment in a tertiary medical center between the years 2019 to 2022 were retrospectively reviewed. Patients included in this study were eligible for biological treatment according to the EPOS 2020 criteria. Among patients who had their first follow-up visit <6 months from the treatment initiation, the Sino-Nasal Outcome Test 22 Questionnaire (SNOT-22) score had decreased by 22% (p= 0.01) and the nasal polyp score (NPS) had decreased by 48% (p= 0.05). Among patients who had their first follow-up visit ≥6 months from treatment initiation, the SNOT-22 score had decreased by 40% (p= 0.03) and the NPS had decreased by 39% (p= 0.1). The number of patients who needed systemic steroid treatment had decreased by 68% (p< 0.0001), and the number of patients who needed endoscopic sinus surgery had decreased by 74% (p< 0.0001). These findings correspond with the improvement of clinical symptoms observed in prior randomized clinical trials, thus showing the effectiveness of biologic medications in the treatment of severe CRSwNP in a real-life setting. Although further cohort studies are warranted, our study also suggests evaluating patients at follow-up visits mainly by quality-of-life aspects and investigating longer dosing intervals of dupilumab.