The potential association between antibiotic use and the risk of rheumatoid arthritis (RA) has drawn significant attention from clinicians and researchers in recent years due to the wild usage of antibiotic. This study aimed to perform a systematic review and meta-analysis of the literature to determine if antibiotic use is associated with an increased risk of RA, so as to provide an important reference for clinical decision-making. Case-control and nest case-control studies of assessing whether antibiotic use is associated with the onset of RA will be identified in searches of 4 databases from their inception to August 2019. All data were assessed and extracted by 2 authors independently. The Newcastle-Ottawa scale was used to assess the quality of the selected studies. Manager Software 5.3 from Cochrane Collaboration (London, UK) and Stata 15.1 (Stata Corp, College Station, TX) will be used to conduct meta-analysis, determining pooled odds ratios and evaluating heterogeneity between studies. The results of this systemic review and meta-analysis will be submitted to a recognized journal for publication. This systemic review and meta-analysis will determine if antibiotic use is associated with an increased risk of RA. We hope this study can make a definitive conclusion for the association.