ObjectiveTo provide real‐life evidence on long‐term radiological changes in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP) treated with dupilumab, and to assess possible differences between radiological and clinical results in terms of endoscopic findings and Patient‐Reported‐Outcomes (PROs).MethodsConsecutive patients treated with dupilumab for recalcitrant CRSwNP were required to undergo CT scan at baseline (T0) and after 12 (T1) since first administration. A group of patients also performed CT scan at 52 weeks (T2) to assess long‐term outcomes. At each timepoint, patients underwent nasal endoscopy, assessment of Nasal‐Polyp‐Score (NPS), Lund‐Kennedy‐Score (LKS), and had to fill in the 22‐item Sinonasal‐Outcome‐Test (SNOT‐22) and Visual‐Analogue‐Scales (VAS) for sinonasal symptoms.ResultsIn fifty‐three included patients, from T0 to T1 we detected a significant reduction in mean Lund‐Mackay score (LM), PROs (SNOT‐22, VAS) and endoscopic (NPS, LKS) scores (p < 0.05). In the subset of patients that reached T2 (n = 30), compared to T1, we observed a further significant decrease in mean LM, SNOT‐22, VAS, and NPS scores, but not in LKS (p = 0.420). At T1, the highest improvement was observed in PROs (SNOT‐22: 56.26%), and polyp size (NPS: 49.83%). Conversely, between T1 and T2, sinus opacification was shown to be the most improved outcome (LM: 36.86%).ConclusionsOur experience showed that poorly controlled CRSwNP patients treated with dupilumab experienced significant improvement in radiologic, endoscopic and clinical disease severity. While in the initial 3 months, PROs garnered attention for showing earlier effectiveness, radiological outcomes revealed sustained and gradual efficacy in a longer term.Level of EvidenceLevel 4. According to the Oxford Center for Evidence‐Based Medicine 2011 level of evidence guidelines, this non‐randomized retrospective cohort study is classified as level 4 evidence Laryngoscope, 2023