The objective of this systematic literature review is to examine the impact of interventions to improve cardiovascular disease healthcare provided to people living in rural areas. Systematic electronic searches were conducted in Medline, CINAHL, Embase, Scopus, and Web of Knowledge in July 2018. We included clinical trials assessing the effectiveness of interventions to improve cardiovascular disease healthcare in rural areas. Study eligibility assessment, data extraction, and critical appraisal were undertaken by two reviewers independently. We identified 18 trials (18 interventions). They targeted myocardial infarction (five interventions), stroke (eight), and heart failure (five). All the interventions for myocardial infarction were based on organizational changes (e.g. implementation of mobile coronary units). They consistently reduced time to treatment and decreased mortality. All the interventions for heart failure were based on the provision of patient education. They consistently improved patient knowledge and self-care behaviour, but mortality reductions were reported in only some of the trials. Among the interventions for stroke, those based on the implementation of telemedicine (tele-stroke systems or tele-consultations) improved monitoring of stroke survivors; those based on new or enhanced rehabilitation services did not consistently improve mortality or physical function; whereas educational interventions effectively improved patient knowledge and behavioural outcomes. In conclusion, a number of different strategies (based on enhancing structures and providing patient education) have been proposed to improve cardiovascular disease healthcare in rural areas. Although available evidence show that these interventions can improve healthcare processes, their impact on mortality and other important health outcomes still remains to be established.