The aim of this systematic review and network meta-analysis is to evaluate the comparative effectiveness of N95, surgical/medical and non-medical facemasks as personal protective equipment against respiratory virus infection. The study incorporated 35 published and unpublished randomized controlled trials and observational studies investigating specific mask effectiveness against influenza virus, SARS-CoV, MERS-CoV and SARS-CoV-2. We searched PubMed, Google Scholar and medRxiv databases for studies published up to 5 February 2021 (PROSPERO registration: CRD42020214729). The primary outcome of interest was the rate of respiratory viral infection. The quality of evidence was estimated using the GRADE approach. High compliance to mask-wearing conferred a significantly better protection (odds ratio [OR], 0.43; 95% confidence interval [CI], 0.23-0.82) than low compliance. N95 or equivalent masks were the most effective in providing protection against coronavirus infections (OR, 0.30; CI, 0.20-0.44) consistently across subgroup analyses of causative viruses and clinical settings. Evidence supporting the use of medical or surgical masks against influenza or coronavirus infections (SARS, MERS and COVID-19) was weak. Our study confirmed that the use of facemasks provides protection against respiratory viral infections in general; however, the effectiveness may vary according to the type of facemask used. Our findings encourage the use of N95 respirators or their equivalents (e.g., P2) for best personal protection in healthcare settings until more evidence on surgical and medical masks is accrued. This study highlights a substantial lack of evidence on the comparative effectiveness of mask types in community settings.