Abstract Background While there is good evidence to show that behavioural and lifestyle interventions can reduce cardiovascular disease risk factors in affluent settings, less evidence exists in lower income settings. This study systematically assesses the evidence on cost-effectiveness for preventive cardiovascular interventions in low and middle-income settings. Methods Design: Systematic review of economic evaluations on interventions for prevention of cardiovascular disease. Data sources: PubMed, Web of Knowledge, Scopus and Embase, Opensigle, the Cochrane database, Business Source Complete, the NHS Economic Evaluations Database, reference lists and email contact with experts. Eligibility criteria for selecting studies: we included economic evaluations conducted in adults, reporting the effect of interventions to prevent cardiovascular disease in low and middle income countries as defined by the World Bank. The primary outcome was a change in cardiovascular disease occurrence including coronary heart disease, heart failure and stroke. Data extraction: After selection of the studies, data were extracted by two independent investigators using a previously constructed tool and quality was evaluated using Drummond’s quality assessment score. Results From 9731 search results we found 16 studies, which presented economic outcomes for interventions to prevent cardiovascular disease in low and middle income settings, with most of these reporting positive cost effectiveness results. When the same interventions were evaluated across settings, within and between papers, the likelihood of an intervention being judged cost effective was generally lower in regions with lowest gross national income. While population based interventions were in most cases more cost effective, cost effectiveness estimates for individual pharmacological interventions were overall based upon a stronger evidence base. Conclusions While more studies of cardiovascular preventive interventions are needed in low and mid income settings, the available high-level of evidence supports a wide range of interventions for the prevention of cardiovascular disease as being cost effective across all world regions.