Background Two previous meta-analyses comparing staples versus sutures have led to conflicting relative risks for surgical site infection between skin closure methods after orthopaedic surgery. Consequently, the choice of sutures or staples for skin closure continues to be a subject of conversation. Recently, additional randomized trials have been published, and an updated meta-analysis is needed to inform this debate. Questions/purposes To determine using a meta-analysis of randomized trials (1) whether there is a difference in surgical site infection (SSI) between staples and sutures for skin closure after orthopaedic surgery, and (2) whether that finding remains the same when the analysis is limited to randomized trials with a low risk of bias. Methods A systematic review and meta-analysis of randomized controlled trials (RCTs) comparing staples with sutures for skin closure after orthopaedic surgery was conducted. We excluded barbed sutures, surgical zippers, and skin adhesives from this meta-analysis. Medline, One of the authors (YRR) received personal fees from Medtronic (Minneapolis, MN, USA) outside the submitted work. Each author certifies that his or her institution waived approval for the reporting of this investigation and that all investigations were conducted in conformity with ethical principles of research.