Background Treatment of postoperative exacerbations with topical antibiotics has grown in popularity due to their ability to administer a high local drug concentration to the sinuses and mitigate systemic side effects. Published literature on the efficacy of topical levofloxacin for treating CRS is scarce. Objective Patients who started levofloxacin 100 mg nasal rinses twice daily following functional endoscopic sinus surgery (FESS) were retrospectively identified. Data collected included rinse duration, bacterial cultures, Sino-Nasal Outcome Test-22 (SNOT-22) scores, Lund-Kennedy (LK) scores, and adverse effects. SNOT and LK scores were compared at 3 time points: pre-operative ( Baseline ), 3 month postoperative pre-rinse ( PostOp ), and at the completion of rinse therapy ( PostRinse ). Analysis of variance (ANOVA) and Wilcoxon rank sum tests were used for pairwise comparisons. Results One hundred and thirty-three patients received levofloxacin rinses for a mean 8.4 ± 18.9 months. On pairwise comparison for LK scores, the difference between PostOp and PostRinse LK scores was −1.0 ± 1.7 ( P < . 001). The change from Baseline to PostOp was −2.0 ± 2.8 ( P < . 001) and the change from Baseline to PostRinse LK scores was −3.2 ± 2.8 ( P < . 001). On pairwise comparison for SNOT scores, significant improvement was observed between Baseline and PostRinse scores (−19.4 ± 20.7, P = . 001) but not between PostOp and PostRinse scores. There was one musculoskeletal adverse event noted. Conclusion Topical levofloxacin rinses afforded a possible benefit in endoscopic appearance of operated sinuses but less definitive benefit in symptom scores. Further, they were safely tolerated with one mild musculoskeletal adverse event.