The authors present national and state-level estimates of effects on medical spending over time of reductions in the prevalence of conditions amenable to primary prevention. Reducing diabetes and hypertension prevalence by 5% nationally would save approximately $8.2 billion annually in the near term. The resulting reductions in comorbidities could bring medium-term savings to approximately $26.8 billion annually. Returns are greatest in absolute terms for private payors, but greatest in percentage terms for public payors. State savings vary with demographic makeup and prevailing morbidity. We conclude that well-designed interventions that achieve improvements in lifestyle-related risk factors could result in sufficient savings to substantially offset intervention costs.