Few simulation models have incorporated the interplay of diabetes, obesity, and cardiovascular disease (CVD); their upstream lifestyle and biological risk factors; and their downstream effects on health disparities and economic consequences. We developed and validated a US Diabetes, Obesity, Cardiovascular Disease Microsimulation (DOC-M) model that incorporates demographic, clinical, and lifestyle risk factors to jointly predict overall and racial-ethnic groups-specific obesity, diabetes, CVD, and cause-specific mortality for the US adult population aged 40 to 79 y at baseline. An individualized health care cost prediction model was further developed and integrated. This model incorporates nationally representative data on baseline demographics, lifestyle, health, and cause-specific mortality; dynamic changes in modifiable risk factors over time; and parameter uncertainty using probabilistic distributions. Validation analyses included assessment of 1) population-level risk calibration and 2) individual-level risk discrimination. To illustrate the application of the DOC-M model, we evaluated the long-term cost-effectiveness of a national produce prescription program. Comparing the 15-y model-predicted population risk of primary outcomes among the 2001-2002 National Health and Nutrition Examination Survey (NHANES) cohort with the observed prevalence from age-matched cross-sectional 2003-2016 NHANES cohorts, calibration performance was strong based on observed-to-expected ratio and calibration plot analysis. In most cases, Brier scores fell below 0.0004, indicating a low overall prediction error. Using the Multi-Ethnic Study of Atherosclerosis cohorts, the c-statistics for assessing individual-level risk discrimination were 0.85 to 0.88 for diabetes, 0.93 to 0.95 for obesity, 0.74 to 0.76 for CVD history, and 0.78 to 0.81 for all-cause mortality, both overall and in three racial-ethnic groups. Open-source code for the model was posted at https://github.com/food-price/DOC-M-Model-Development-and-Validation. The validated DOC-M model can be used to examine health, equity, and the economic impact of health policies and interventions on behavioral and clinical risk factors for obesity, diabetes, and CVD. We developed a novel microsimula'tion model for obesity, diabetes, and CVD, which intersect together and - critically for prevention and treatment interventions - share common lifestyle, biologic, and demographic risk factors.Validation analyses, including assessment of (1) population-level risk calibration and (2) individual-level risk discrimination, showed strong performance across the overall population and three major racial-ethnic groups for 6 outcomes (obesity, diabetes, CVD, and all-cause mortality, CVD- and DM-cause mortality)This paper provides a thorough explanation and documentation of the development and validation process of a novel microsimulation model, along with the open-source code (https://github.com/food-price/ DOCM_validation) for public use, to serve as a guide for future simulation model assessments, validation, and implementation.