Sore throat is a common condition caused by viruses or bacteria, and is a leading cause of antibiotic prescription in primary care. The most common bacterial species is group A streptococcus ('strep throat'). Between 50% to 70% of pharyngitis cases are treated with antibiotics, despite the majority of cases being viral in origin. One strategy to reduce antibiotics is to use rapid tests for group A streptococcus to guide antibiotic prescriptions. Rapid tests can be used alone or in combination with a clinical scoring system. To assess the efficacy and safety of strategies based on rapid tests to guide antibiotic prescriptions for sore throat in primary care settings. We searched CENTRAL, MEDLINE, Embase, CINAHL, Web of Science, and LILACS, as well as the trial registries ClinicalTrials.gov and the WHO ICTRP on 5 June 2019. We included randomised controlled trials (RCTs) comparing rapid tests with management based on clinical grounds to guide the prescription of antibiotics for people with a sore throat in ambulatory care settings. We included trials that randomised individuals, as well as cluster-RCTs in which individual practitioners (or practices) or emergency departments were randomised. Two review authors independently extracted data on the primary outcomes (number of participants provided with an antibiotic prescription; number of participants with an antibiotic dispensed) and secondary outcomes (duration of sore throat symptoms; duration of other symptoms; quality of life measures; number of participants with a complication attributed to the index infection; number of participants in need of re-consultation by the end of follow-up; number of participants in need of hospital admission by the end of follow-up; number of satisfied participants; number of participants with an adverse event attributed to the rapid test). We assessed the risk of bias of all included trials and used GRADE to assess the certainty of the evidence. We performed meta-analyses and sensitivity analyses when feasible. We included five trials (2891 children and adult participants in total; 2545 participants after adjusting for clustering). Management in the intervention group was as follows: in three trials rapid tests were used in combination with a clinical scoring system; in one trial, some physicians were asked to use rapid tests alone, while others were asked to use rapid tests in combination with a clinical scoring system; in one trial, rapid tests were used alone. Based on data from five trials (2545 participants), a large reduction in prescribed antibiotics was found in the rapid test group (481/1197) versus management based on clinical grounds (865/1348), for a summary risk difference (RD) of -25%, 95% confidence interval (CI) -31% to -18%; I2 = 62%; moderate-certainty evidence. Estimates of effect on antibiotic prescription rates were stable in various sensitivity analyses. Based on data from two trials (900 people) originating from the same overarching study, the evidence suggests that rapid tests may not reduce dispensed antibiotic treatments: rapid test group (156/445) versus management based on clinical grounds (197/455); summary RD -7%, 95% CI -17% to 2%; I2 = 53%; low-certainty evidence. Four trials (2075 participants) reported data on the number of participants with a complication attributed to the index infection; the summary odds ratio (OR) was 0.85, 95% CI 0.03 to 26.65; P = 0.93; I2 = 62%; very low-certainty evidence, which means that people in the rapid testing group were less likely to develop complications of the index infection, but the evidence is very uncertain. Two trials (1161 participants) reported on the number of participants in need of re-consultation by the end of follow-up; the summary OR was 1.12, 95% CI 0.57 to 2.21; P = 0.74; I2 = 59%; low-certainty evidence, which means that participants in the rapid testing group were more likely to be in need of re-consultation by the end of the study follow-up, but the evidence is uncertain. Lack of data impeded assessment of other secondary outcomes (including safety outcomes) and of sources of heterogeneity. AUTHORS' CONCLUSIONS: Rapid testing to guide antibiotic treatment for sore throat in primary care probably reduces antibiotic prescription rates by 25% (absolute risk difference), but may have little or no impact on antibiotic dispensing. More studies are needed to assess the efficacy and safety of rapid test-guided antibiotic prescribing, notably to evaluate patient-centred outcomes and variability across subgroups (e.g. adults versus children). Copyright © 2020 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.