The management of refractory chronic rhinosinusitis (CRS) after endoscopic sinus surgery is complex and challenging. We conducted a prospective clinical pilot study to evaluate the effectiveness of a rhinotopic protocol for the treatment of refractory CRS. Our study population was made up of 20 patients-8 men and 12 women, aged 31 to 76 years (mean: 50.1)-who were treated in our tertiary care rhinology fellowship training program. The rhinotopic protocol consisted of twice-daily saline rinses, each of which was followed by the administration of a nebulized corticosteroid and then a nebulized antibiotic. This regimen was administered for 6 weeks. Thereafter, patients underwent a once-weekly endoscopic sinus debridement followed by topical intrasinus installation of a corticosteroid and antibiotic. The duration of follow-up was 24 weeks, and thus the total study duration was 30 weeks. Treatment outcomes were based on Lund-Kennedy symptom scores and Lund-Kennedy endoscopic appearance scores. We found a 56% improvement in the mean symptom score after 3 weeks of therapy and 77% after 6 weeks. Subsequent follow-up revealed 90% improvement 4 weeks following the completion of therapy and 95% at 8 weeks post-therapy. Thereafter, we saw a small decrease in improvement: 73% at 16 weeks of follow-up and 65% at 24 weeks. Analysis of endoscopic appearance scores revealed a 55% improvement at 3 weeks of therapy and 84% at 6 weeks. The same general pattern emerged during follow-up, with 94% improvement 4 weeks after the cessation of therapy, 96% at 8 weeks, 76% at 16 weeks, and 75% at 24 weeks. Sinus cultures performed 4 weeks after the cessation of therapy found no growth in 13 patients (65%), normal respiratory flora in 5 patients (25%), a persistent pathogen in 1 patient (5%), and the emergence of a new pathogen in another (5%). Analysis of symptom scores and endoscopic appearance scores revealed that the rhinotopic protocol resulted in statistically significant improvement (p < 0.001) throughout the treatment period and follow-up period, although the improvement gradually declined over time. We therefore conclude that a rhinotopic protocol can be an effective treatment for refractory CRS.