Objectives To assess the impact of allergy on clinical presentations (phenotypes) and inflammatory patterns (endotypes) of chronic rhinosinusitis with nasal polyps (CRSwNP). Methods A single-center prospective study was conducted over an 18-month period. Fifty-seven patients with refractory CRSwNP were included. The diagnosis of allergy was based on concordant skin prick tests and symptoms. Phenotypes were determined on symptom severity score, polyp size classification and Lund-Mackay CT staging. Inflammatory endotypes were determined on biomarker analysis (IgE, IgA, IL-5, IL-9, ECP, EDN) in blood and nasal secretions. Eosinophil counts were obtained in blood, nasal secretions and polyps. Results Phenotype and endotype profiles were comparable in patients with (n = 15) or without (n = 42) allergy. Only asthma with high total IgE blood concentration showed association with allergy. Conclusions The present results suggest that allergy is not directly involved in the clinical expression and specific inflammatory pathways of CRSwNP. New therapies target inflammation signaling pathways, and identifying accurate blood and tissue biomarkers will be the line of research most likely to improve treatment of CRSwNP.