Background: Many chronic rhinosinusitis (CRS) treatment regimes revolve around "one-off" maximal medical therapy (MMT) protocols, and although many patients initially respond, long-term control is unpredictable. The value of imaging, endoscopy, and patient progress after MMT for CRS is assessed. Methods: Symptomatic CRS patients with computed tomography (CT)-confirmed disease were recruited at a tertiary rhinology clinic. All patients received at least a 3-week oral prednisone course as part of their MMT. Pretreatment and posttreatment nasal symptoms scores (NSS), quality of life (22-item SinoNasal Outcomes Test [SNOT-22]), and CT (Lund-Mackay [LM]) scores were recorded along with post-MMT endoscopy status. Results: A total of 86 patients (38% female, age 46 ± 13 years) met inclusion criteria. Pre-MMT and post-MMT LM scores were 10.9 ± 5.3 and 8.3 ± 5.5 (change 2.6 ± 3.8, p < 0.001). Median follow-up after their initial post-MMT assessment was 6.3 (interquartile range [IQR] 17) months. At initial post-MMT review, 43 (50%) were symptomatic with persistent radiologic disease ("symptomatic CRS"), 12 (14%) were asymptomatic with no radiologic disease ("resolved CRS"), 21 (24%) were asymptomatic with persistent radiologic disease ("asymptomatic CRS"), and 10 (12%) were symptomatic with no radiologic disease ("alternate diagnosis"). Pre-MMT NSS and SNOT-22 were similar among groups. The "asymptomatic CRS" group had the highest age (52 ± 11 years, p = 0.07). The "alternate diagnosis" group had the lowest initial LM scores (5.2 ± 2.9, p = 0.001). Of the "asymptomatic CRS" patients, 43% relapsed between 3 and 23 months (median 6; IQR 4.4 months) post-MMT and 29% eventually underwent surgery. Conclusion: Although MMT for CRS achieved symptomatic relief in 38% patients, objective evidence of disease was associated with clinical relapse. The concepts of "response" to medical therapy and the need to "control" long-term inflammatory burden need to be balanced.