This study investigated the relationship between sinonasal inflammatory involvement according to the computed tomography (CT) staging system (Lund–Mackay score) with clinical, laboratory, histopathological and prognostic features of chronic rhinosinusitis with nasal polyps (CRSwNP). Seventy-eight patients with CRSwNP who had undergone surgery were enrolled. Total (p = 0.0062), ethmoid (p = 0.0496), sphenoid (p = 0.0335), ostiomeatal complex (OMC) (p = 0.0235) and frontal (p = 0.0164) CT scores were predictive of non-steroidal anti-inflammatory drugs-exacerbated respiratory disease (NERD) in the univariate analysis. Total (p = 0.0022), ethmoid (p = 0.0290), sphenoid (p = 0.0370), frontal (p = 0.0116), maxillary (p = 0.0357) and OMC (p = 0.0058) CT scores were predictve of asthma at the univariate analysis. No significant differences were found between patients with vs. without allergy in terms of total and partial CT scores. High blood eosinophil counts (>0.24 vs. ≤0.24 cells × 109/L) resulted in being associated with total (p = 0.0213), maxillary (p = 0.0227) and ethmoid (p = 0.0491) CT scores in the univariate analysis. Higher ethmoid (p = 0.0006) and total sinonasal (p = 0.0027) CT scores were found to predict histopathologically eosinophil CRSwNPs in the univariate analysis. CT scores did not result as predictive of NSAID-exacerbated respiratory disease, asthma, or blood eosinophil count at the multivariate analysis. Risk of relapse was related to the presence of NERD (p = 0.0207, HR [95% CI] 3.914 [1.232–12.435]), higher preoperative total (HR = 1.098 95%CI: 1.001–1.204, p = 0.0486) and frontal sinus CT scores (HR = 1.555 95%CI: 1.006–1.886, p = 0.0218), but these results were not confirmed by the multivariable analysis. Sinonasal CT scores showed significant differences in this heterogeneous inflammatory condition. Identifying CRSwNP characteristics is necessary to avoid generic treatments with poor outcomes.