This systematic review and meta-analysis quantified the protective effect of facemasks and respirators against respiratory infections among healthcare workers. Relevant articles were retrieved from Pubmed, EMBASE, and Web of Science. Meta-analyses were conducted to calculate pooled estimates. Meta-analysis of randomized controlled trials (RCTs) indicated a protective effect of masks and respirators against clinical respiratory illness (CRI) (risk ratio [RR] = 0.59; 95% confidence interval [CI]:0.46-0.77) and influenza-like illness (ILI) (RR = 0.34; 95% CI:0.14-0.82). Compared to masks, N95 respirators conferred superior protection against CRI (RR = 0.47; 95% CI: 0.36-0.62) and laboratory-confirmed bacterial (RR = 0.46; 95% CI: 0.34-0.62), but not viral infections or ILI. Meta-analysis of observational studies provided evidence of a protective effect of masks (OR = 0.13; 95% CI: 0.03-0.62) and respirators (OR = 0.12; 95% CI: 0.06-0.26) against severe acute respiratory syndrome (SARS). This systematic review and meta-analysis supports the use of respiratory protection. However, the existing evidence is sparse and findings are inconsistent within and across studies. Multicentre RCTs with standardized protocols conducted outside epidemic periods would help to clarify the circumstances under which the use of masks or respirators is most warranted.