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Background SARS-CoV-2 antigen rapid diagnostic tests (Ag-RDTs) are increasingly being integrated in testing strategies around the world. Studies of the Ag-RDTs have shown variable performance. In this systematic review and meta-analysis, we assessed the clinical accuracy (sensitivity and specificity) of commercially available Ag-RDTs. Methods and findings We registered the review on PROSPERO (registration number: CRD42020225140). We systematically searched multiple databases (PubMed, Web of Science Core Collection, medRvix, bioRvix, and FIND) for publications evaluating the accuracy of Ag-RDTs for SARS-CoV-2 up until 30 April 2021. Descriptive analyses of all studies were performed, and when more than 4 studies were available, a random-effects meta-analysis was used to estimate pooled sensitivity and specificity in comparison to reverse transcription polymerase chain reaction (RT-PCR) testing. We assessed heterogeneity by subgroup analyses, and rated study quality and risk of bias using the QUADAS-2 assessment tool. From a total of 14,254 articles, we included 133 analytical and clinical studies resulting in 214 clinical accuracy datasets with 112,323 samples. Across all meta-analyzed samples, the pooled Ag-RDT sensitivity and specificity were 71.2% (95% CI 68.2% to 74.0%) and 98.9% (95% CI 98.6% to 99.1%), respectively. Sensitivity increased to 76.3% (95% CI 73.1% to 79.2%) if analysis was restricted to studies that followed the Ag-RDT manufacturers’ instructions. LumiraDx showed the highest sensitivity, with 88.2% (95% CI 59.0% to 97.5%). Of instrument-free Ag-RDTs, Standard Q nasal performed best, with 80.2% sensitivity (95% CI 70.3% to 87.4%). Across all Ag-RDTs, sensitivity was markedly better on samples with lower RT-PCR cycle threshold (Ct) values, i.e., Lukas Brümmer and co-workers report on the accuracy of rapid antigen tests for SARS-CoV-2., Author summary Why was this study done? Antigen rapid diagnostic tests (Ag-RDTs) are considered an important diagnostic tool to fight the spread of SARS-CoV-2. An increasing number of Ag-RDTs are offered on the market, and a constantly growing body of literature evaluating their performance is available. To inform decision makers about the best test to choose, an up-to-date summary of their performance is needed. What did the researchers do and find? On a weekly basis, we search multiple databases for evaluations of Ag-RDTs detecting SARS-CoV-2 and post the results on https://www.diagnosticsglobalhealth.org. Based on the search results up until 30 April 2021, we conducted a systematic review and meta-analysis, including a total of 133 clinical and analytical accuracy studies. Across all meta-analyzed studies, when Ag-RDTs were performed according to manufacturers’ recommendations, they showed a sensitivity of 76.3% (95% CI 73.1% to 79.2%), with LumiraDx (sensitivity 88.2% [95% CI 59.0% to 97.5%]) and, of the instrument-free Ag-RDTs, Standard Q nasal (74.9% sensitivity [95% CI 69.3% to 79.7%]) performing best. Across all Ag-RDTs, sensitivity increased to 95.8% (95% CI 92.3% to 97.8%) when we restricted the analysis to samples with high viral loads (i.e., a Ct value < 25) and to 83.8% (95% CI 76.3% to 89.2%) when tests were performed on patients within the first week after symptom onset. What do these findings mean? Ag-RDTs detect the vast majority of cases within the first week of symptom onset and those with high viral load. Thus, they can have high utility for diagnostic purposes in the early phase of disease. Out of all assessed tests, LumiraDx showed the highest accuracy. Standard Q was the best-performing test when only considering those that do not require an instrument. A standardization of reporting methods for clinical accuracy studies would enhance future test comparisons.