OBJECTIVES::  This study aims to estimate the current and future burden of cardiovascular diseases (CVD) in Colombia, and quantify the impact of reducing modifiable risk factors. METHODS::  A burden of disease model was used to forecast the burden of CVD in Colombia, and estimate the impact of reducing modifiable risk factors (tobacco use, hypertension, type 2 diabetes, obesity and physical inactivity) in the general Colombian population, in accordance with World Health Organization (WHO) targets. Another model estimated the impact of reducing LDL-cholesterol through increased access to effective treatment for two high risk populations: heterozygous familial hypercholesterolemia (HeFH) and secondary prevention (SP), with a focus on patients with LDL-cholesterol >100 mg/dL. Inputs for the models included disease and risk factor prevalence, population forecast, CVD event rates, and treatment effectiveness, primarily derived from the published literature. Direct costs to the public health care system and indirect costs from lost production due to premature mortality, hospitalizations, and absenteeism were included, although the cost of programs and pharmacological interventions to reduce risk factors was not considered. RESULTS::  The prevalence of CVD is projected to increase to 1.6 million by 2035, while the economic burden, including both direct and indirect costs, would increase to US$14 billion. The value of reducing modifiable risk factors (except LDL-cholesterol) is estimated at US$10.5 billion over the forecast period. Similarly, the value of reducing LDL-cholesterol through increased access to effective treatment would be up to US$1.5 billion for HeFH patients and up to US$9.2 billion for SP patients over the forecast period. CONCLUSIONS::  The burden of CVD is significant and growing. Efforts to achieve WHO risk factor targets and further lower LDL-cholesterol through increased access to effective treatment for high-risk patients are projected to greatly reduce the clinical, economic, and humanistic burden of cardiovascular disease in Colombia.