OBJECTIVE： To compare the efficacy and safety of dirithromycin and cefixime in the treatment of chronic rhinosinusitis （CRS）. METHODS： 149 CRS patients were randomly divided into control group （77 cases） and observation group （72 cases）. Control group was orally given Cefixime dispersible tablet 0.2 g， twice a day， for 2 weeks. Observation group was orally given Dirithromycin enteric-coated tablet 0.25 g， once a day， for 2 weeks. Clinical efficacy， sign and symptom score before and after treatment， and the incidence of adverse reactions in 2 groups were observed. RESULTS： There were 5 patients lost in follow-up in observation group，and 4 in control group. There were no significant differences in the total effective rate and the incidence of adverse reactions in 2 groups （P＞0.05）. After treatment， the sign and symptom scores in 2 groups were significantly lower than before， and observation group was lower than control group， with statistical significance （P＜0.05）. CONCLUSIONS： Dirithromycin and cefixime have similar efficacy and safety in the treatment of CRS， while dirithromycin is superior to cefixime in terms of improving clinical symptoms of patients.