Objective To evaluate the effectiveness and safety of clarithromycin extended-release and immediate-release formulations in the treatment of patients with acute exacerbation of chronic bronchitis. Methods The randomized controlled trials (RCTs) of clarithromycin extended-release and immediate-release formulations in the treatment of patients with acute exacerbation of chronic bronchitis were searched in the following electronic databases: The Cochrane Library (Issue 1, 2010), PubMed (2000 to Jan. 2010), EMbase (1980 to Dec. 2009), CBM (2000 to Jan. 2010), and WanFang Data (2000 to Jan. 2010). Two reviewers independently screened the included studies, abstracted the data and assessed the quality. The RevMan 5.0 software was used to conduct meta-analyses. Results A total of four RCTs involving 2041 patients were included, and the Jadad scales of all studies were more than five. The results of meta-analyses showed that there was no significant difference between the extended-release formulation group and the immediate-release formulation group in aspects of the clinical cure rate (RR=0.93, 95%CI 0.96 to 1.03), the pathogen eradication rate (RR=0.99, 95%CI 0.94 to 1.04), and the adverse reaction incidence rate (RR=1.06, 95%CI 0.90 to 1.25). Conclusion As the present evidence shows, there is no significant difference in effectiveness and safety between the clarithromycin extended-release and immediate-release formulations in the treatment of patients with acute exacerbation of chronic bronchitis.