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Introduction: The strength and dose-response relationship between fruit and vegetable intake and mortality are still subjects of debate.Hypothesis: We hypothesized that higher fruit and vegetable intake was associated with lower total and cause-specific mortality in a nonlinear dose-response manner.Methods: We followed 66,719 women from the Nurses’ Health Study (1984-2012) and 42,016 men from the Health Professionals Follow-up Study (1986-2012) who were free from cardiovascular disease (CVD), cancer and diabetes at baseline. Diet was assessed using food frequency questionnaires at baseline and updated every 2 to 4 years.Results: Our study documented 28,333 deaths during follow-up. The 3rd quintile of fruit and vegetable intake was associated with the lowest hazard ratio (HR) of total mortality (HR, 0.87, 95% CI, 0.83-0.90, Pnonlinear <0.001) compared to the 1st quintile. The nonlinear dose-response relationship plateaued at about 5 servings/day (svg/d), but above that level, higher intake was not associated with additional risk reduction. We found similar nonlinear associations for CVD, cancer and respiratory disease mortality. Compared to fruit and vegetable intake <1.5 svg/d, the intake level ≥5 svg/d was associated with HRs (95% CI) of 0.84 (0.75-0.93), 0.82 (0.72-0.93) and 0.55 (0.44-0.67) for cancer, CVD and respiratory disease mortality, respectively. Among individual fruits and vegetables, the associations of intakes with mortality were heterogeneous. Higher intakes of most fruit and vegetable subgroups were associated with lower total mortality, whereas higher intake of starchy vegetable such as peas and corn was not associated with total mortality.Conclusions: Higher fruit and vegetable intake was associated with lower mortality; the lowest mortality was observed among those who consumed 5 servings of fruit and vegetables per day (2 servings of fruit and 3 servings of vegetables daily). Our findings also suggest the presence of heterogeneity in the health benefits of individual fruits and vegetables.