BackgroundThe effectiveness of audit and feedback (A&F) interventions to improve compliance to healthcare guidelines is supported by randomised controlled trials (RCTs) and meta-analyses of RCTs. However, there is currently a knowledge gap on their cost-effectiveness.ObjectiveWe aimed to assess whether A&F interventions targeting improvements in compliance to recommended care are economically favourable.MethodsWe conducted a systematic review including experimental, observational and simulation-based economic evaluation studies of A&F interventions targeting healthcare providers. Comparators were a ‘do nothing’ strategy, or any other intervention not involving A&F or involving a subset of A&F intervention components. We searched MEDLINE, CINAHL, CENTRAL, Econlit, EMBASE, Health Technology Assessment Database, MEDLINE, NHS Economic Evaluation Database, ABI/INFORM, Web of Science, ProQuest and websites of healthcare quality associations to December 2021. Outcomes were incremental cost-effectiveness ratios, incremental cost-utility ratios, incremental net benefit and incremental cost-benefit ratios. Pairs of reviewers independently selected eligible studies and extracted relevant data. Reporting quality was evaluated using CHEERS (Consolidated Health Economic Evaluation Reporting Standards). Results were synthesised using permutation matrices for all studies and predefined subgroups.ResultsOf 13 221 unique citations, 35 studies met our inclusion criteria. The A&F intervention was dominant (ie, at least as effective with lower cost) in 7 studies, potentially cost-effective in 26 and was dominated (ie, the same or less effectiveness and higher costs) in 2 studies. A&F interventions were more likely to be economically favourable in studies based on health outcomes rather than compliance to recommended practice, considering medical costs in addition to intervention costs, published since 2010, and with high reporting quality.DiscussionResults suggest that A&F interventions may have a high potential to be cost-effective. However, as is common in systematic reviews of economic evaluations, publication bias could have led to an overestimation of their economic value.