Background: The Million Hearts Cardiovascular Disease Risk Reduction Model provides financial incentives for practices to lower 10-year atherosclerotic cardiovascular disease (ASCVD) risk for high-risk (ASCVD ≥30%) Medicare patients. To estimate average practice-level ASCVD risk reduction, we applied optimal trial outcomes to a real-world population with high ASCVD risk. Methods: This study uses observational registry data from the National Cardiovascular Data Registry Practice Innovation and Clinical Excellence Registry from January 2013 to June 2016. We modeled ASCVD risk reductions using historical clinical trial data (reducing cholesterol by 26.5%, reducing systolic blood pressure by 10.9%, reducing smoking rates by 21.8%) the average reduction in ASCVD risk associated with individual and combined risk factor modifications, and then percentage of practices achieving the various incentive thresholds for the Million Hearts Model. Results: The final study population included 135 166 patients, with 16 248 (12.0%) with 10-year ASCVD risk of ≥30%, but without existing ASCVD. The mean 10-year ASCVD risk was 41.9% (±1 SD of 11.6). Using risk factor reductions from clinical trials, lowering cholesterol, blood pressure, and smoking rates reduced 10-year ASCVD risk by 3.3% (±3.1), 6.3% (±1.1) and 0.5% (±1.3), respectively. Combining all 3 reductions resulted in a 9.7% (±3.6) reduction, with 67 (27.0%) of practices achieving a patient-level average 10-year ASCVD risk reduction of ≥10%, 181 (73.0%) achieving a 2 to 10% reduction, and no practice achieving <2% reduction. Conclusions: In cardiology practices, about 1 out of 8 patients have a 10-year ASCVD risk ≥30% and qualify as high risk in the Million Hearts Model. If practices target the three main modifiable risk factors and achieve reductions similar to clinical trial results, ASCVD risk could be substantially lowered and all practices could receive incentive payments. These findings support the potential benefit of the Million Hearts Model and provide guidance to participating practices.