ABSTRACT: Few comprehensive cardiovascular risk reduction programs, particularly those in rural, low-income communities, have sustained community-wide interventions for more than 10 years and demonstrated the effect of risk factor improvements on reductions in morbidity and mortality.To document health outcomes associated with an integrated, comprehensive cardiovascular risk reduction program in Franklin County, Maine, a low-income rural community.Forty-year observational study involving residents of Franklin County, Maine, a rural, low-income population of 22,444 in 1970, that used the preceding decade as a baseline and compared Franklin County with other Maine counties and state averages.Community-wide programs targeting hypertension, cholesterol, and smoking, as well as diet and physical activity, sponsored by multiple community organizations, including the local hospital and clinicians.Resident participation; hypertension and hyperlipidemia detection, treatment, and control; smoking quit rates; hospitalization rates from 1994 through 2006, adjusted for median household income; and mortality rates from 1970 through 2010, adjusted for household income and age.More than 150,000 individual county resident contacts occurred over 40 years. Over time, as cardiovascular risk factor programs were added, relevant health indicators improved. Hypertension control had an absolute increase of 24.7% (95% CI, 21.6%-27.7%) from 18.3% to 43.0%, from 1975 to 1978; later, elevated cholesterol control had an absolute increase of 28.5% (95% CI, 25.3%-31.6%) from 0.4% to 28.9%, from 1986 to 2010. Smoking quit rates improved from 48.5% to 69.5%, better than state averages (observed?-?expected [O?-?E], 11.3%; 95% CI, 5.5%-17.7%; P?