Substantial variation in economic analyses of cardiovascular disease management programs hinders not only the proper assessment of cost-effectiveness but also the identification of heterogeneity of interest such as patient characteristics. The authors discuss the impact of reporting and methodological variation on the cost-effectiveness of cardiovascular disease management programs by introducing issues that could lead to different policy or clinical decisions, followed by the challenges associated with net intervention effects and generalizability. The authors conclude with practical suggestions to mitigate the identified issues. Improved transparency through standardized reporting practice is the first step to advance beyond one-off experiments (limited applicability outside the study itself). Transparent reporting is a prerequisite for rigorous cost-effectiveness analyses that provide unambiguous implications for practice: what type of program works for whom and how.