Abstract Objective To examine the effectiveness of physical activity interventions delivered or prompted by primary care health professionals for increasing moderate to vigorous intensity physical activity (MVPA) in adult patients. Design Systematic review and meta-analysis of randomised controlled trials. Data sources Databases (Medline and Medline in progress, Embase, PsycINFO, CINAHL, SPORTDiscus, Sports Medicine and Education Index, ASSIA, PEDro, Bibliomap, Science Citation Index, Conference Proceedings Citation Index), trial registries (Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, TRoPHI), and grey literature (OpenGrey) sources were searched (from inception to September 2020). Eligibility criteria for selecting studies Randomised controlled trials of aerobic based physical activity interventions delivered or prompted by health professionals in primary care with a usual care control group or another control group that did not involve physical activity. Study selection and analysis Two independent reviewers screened the search results, extracted data from eligible trials and assessed the risk of bias using the Cochrane risk of bias tool (version 2). Inverse variance meta-analyses using random effects models examined the primary outcome of difference between the groups in MVPA (min/week) from baseline to final follow-up. The odds of meeting the guidelines for MVPA at follow-up were also analysed. Results 14 566 unique reports were identified and 46 randomised controlled trials with a range of follow-ups (3-60 months) were included in the meta-analysis (n=16 198 participants). Physical activity interventions delivered or prompted by health professionals in primary care increased MVPA by 14 min/week (95% confidence interval 4.2 to 24.6, P=0.006). Heterogeneity was substantial (I ² =91%, P<0.001). Limiting analyses to trials that used a device to measure physical activity showed no significant group difference in MVPA (mean difference 4.1 min/week, 95% confidence interval −1.7 to 9.9, P=0.17; I ² =56%, P=0.008). Trials that used self-report measures showed that intervention participants achieved 24 min/week more MVPA than controls (95% confidence interval 6.3 to 41.8, P=0.008; I ² =72%, P<0.001). Additionally, interventions increased the odds of patients meeting guidelines for MVPA by 33% (95% confidence interval 1.17 to 1.50, P<0.001; I ² =25%, P=0.11) versus controls. 14 of 46 studies were at high risk of bias but sensitivity analyses excluding these studies did not alter the results. Conclusions Physical activity interventions delivered or prompted by health professionals in primary care appear effective at increasing participation in self-reported MVPA. Such interventions should be considered for routine implementation to increase levels of physical activity and improve health outcomes in the population. Systematic review registration PROSPERO CRD42021209484.