Central compartment atopic disease (CCAD) is a variant of chronic rhinosinusitis (CRS) with nasal polyps (CRSwNP) characterized by polypoid changes of the superior nasal septum, middle (MT), and/or superior turbinates (ST). This study evaluates surgical outcomes in patients with CCAD compared with other CRSwNP subtypes. Retrospective analysis was performed at Emory University from May 2012 to November 2019. Patients undergoing primary endoscopic sinus surgery (ESS) for CCAD, aspirin-exacerbated respiratory disease (AERD), allergic fungal rhinosinusitis (AFRS), and CRSwNP not otherwise specified (CRSwNP NOS) were included consecutively, beginning with the earliest date of CCAD patient. Outcome measures included polyp recurrence, revision ESS, oral steroid use, and oral antibiotic use. Pearson chi-square and univariate analysis of variance (ANOVA) were performed for group comparisons. Data was collected for 132 patients (CCAD=38, AERD=20, AFRS=37, CRSwNP NOS=37; 58 females, mean age 42.9 years [range, 13-85 years]). CCAD patients demonstrated polyp recurrence less frequently than expected, whereas AFRS patients had polyp recurrence more frequently than expected (p=0.003; phi 0.32). CCAD patients underwent revision ESS less frequently than expected; AFRS and CRSwNP NOS underwent revision ESS more frequently than expected (p=0.03; phi 0.26). CRSwNP NOS patients received more total antibiotic courses than those with CCAD (p=0.01; eta-squared 0.09) and more courses of antibiotics per month than those with AFRS (p=0.03; eta-squared 0.07). There was no significant difference in follow-up measures across groups (number of visits, total months, or visits per month). Rates of polyp recurrence and revision ESS were significantly lower in CCAD patients compared with patients with other CRSwNP subtypes, suggesting durable benefit of ESS and postoperative medical therapy in CCAD patients.