Research is crucial to implement evidence-based health interventions for control of non-communicable diseases (NCDs). This study aims to assess main features of randomized controlled trials (RCTs) for control of NCDs, and to identify gaps in clinical research on NCDs between high-income and less developed countries. The study included 1177 RCTs in 82 Cochrane Systematic reviews (CSRs) and evaluated interventions for adults with hypertension, diabetes, stroke, or heart diseases. Multivariate logistic regression analyses were conducted to explore factors associated with risk of bias in included RCTs. We found that 78.2% of RCTs of interventions for major NCDs recruited patients in high-income countries. The number of RCTs included in the CSRs was increasing over time, and the increasing speed was more noticeable for RCTs conducted in middle-income countries. RCTs conducted in less developed countries tended to be more recently published, less likely to be published in English, with smaller sample sizes, and at a higher risk of bias. In conclusion, there is still a lack of research evidence for control of NCDs in less developed countries. To brace for rising NCDs and avoid waste of scarce research resources, not only more but also higher quality clinical trials are required in low-and-middle-income countries.