Background: There is growing interest in the relationship between exposure to greenness and health. However, very few studies have evaluated the potential modification of this relationship by the degree of urbanity. We aimed to examine the association between exposure to greenness and mortality in a French cohort, according to urban and rural areas. Methods: We used data from the population-based Gazel cohort with a follow up of 26 years, which enrolled 20,625 participants in 1989. We assigned the satellite-derived Normalised Difference Vegetation Index (NDVI) in different buffers (100, 300, 500 and 1000m) around participants’ residential addresses during follow up. We used the extended Cox proportional hazard model to estimate the association between long-term exposure to greenness and natural mortality with a 10-year lag, after adjusting for relevant covariates including sex, age, alcohol use, smoking status, BMI⋯ Stratified analyses were conducted by urban-rural areas and sex. Results: Among the 19,851 participants eligible in this study [mean age at enrollment 43.7 years (SD 3.5), 73% males], we registered 1847 deaths. Each 0.1 increase in NDVI at 100m was associated with 6% higher mortality rate regardless the type of area [Hazard Ratio (HR)=1.06, 95%CI: 1.03-1.10]. Within population subsets, we found 23% higher mortality rate in rural areas (HR=1.23, 95%CI: 1.15-1.31), but 2% lower mortality rate in urban areas (HR=0.98, 95%CI: 0.93-1.04), with a significant difference of the estimates (P<0.001). These urban-rural differences were slightly amplified by sex, with higher HRs for males in rural areas and lower in urban areas. Results were similar for the other buffers.Conclusions: Greenness exposure was associated with higher mortality risk in rural areas with some indications of a potentially protective association in urban areas. Our study suggests a potential effect modification by urban-rural areas, which may provide relevant information for future research and policy developments.