ObjectiveTo systematically review the efficacy and safety of respiratory fluoroquinolones monotherapy versus β-lactams plus macrolides combination therapy for non-ICU hospitalized community acquired pneumonia (CAP) patients. MethodsWe searched databases including PubMed, the Cochrane Library (Issue 3, 2015), EMbase, CNKI, WanFang Data, VIP and CBM to identify randomized controlled trials (RCTs) involving the comparison of fluoroquinolones monotherapy with β-lactams plus macrolides combination treatment for the non-ICU hospitalized patients with CAP up to April 2015. Two reviewers independently screened literature according to the inclusion and exclusion criteria, extracted data, assessed the risk bias of included studies, and then meta-analysis was performed using the RevMan 5.0 software. ResultsA total of 17 RCTs involving 5 423 patients were included. The results of meta-analysis showed that there was no significant difference between the two therapy groups on the mortality. For the clinical treatment success rates, no significant differences between the two groups were found based on the data of intention-to-treat (ITT) and per-protocol (PP) analyses. However, respiratory fluoroquinolones monotherapy was associated with higher clinical treatment success rates based on the data that it was unclear whether ITT or PP analysis was used (RR=1.08, 95% CI 1.01 to 1.18, P=0.02), especially in Asians (RR=1.10, 95%CI 1.02 to 1.18, P=0.01). Additionally, respiratory fluoroquinolones monotherapy was associated with less adverse events (RR=0.81, 95%CI 0.73 to 0.90, P<0.000 1), especially in Caucasians (RR=0.64, 95%CI 0.36 to 1.14, P=0.13). ConclusionCurrent evidence shows that the efficacy of respiratory fluoroquinolones monotherapy may be similar to β-lactams plus macrolides combination treatment for non-ICU hospitalized CAP patients. Since the limitation of quantity and quality of included studies, large-scale high-quality RCTs are needed to verify the above conclusion.