Introduction: Epigenetic age is a marker of healthy lifespan. Diet quality is known to be associated with the risk of developing chronic diseases; however, the relation between diet quality and epigenetic age remains to be investigated. Hypothesis: We tested the hypothesis that healthy diet quality is associated with favorable epigenetic age. Methods: Participants were drawn from the eighth examination of the Framingham Heart Study Offspring cohort ( n =1,995; mean age 67 years; 55% women). Diet quality was estimated using Alternative Healthy Eating Index (AHEI) and Mediterranean-style Diet Score (MDS) derived from food frequency questionnaire. A second generation of epigenetic age, DNA methylation GrimAge, was calculated. Epigenetic age acceleration (GrimAA) was derived as residual after adjustment for chronological age using linear regression model. Results and Conclusions: Higher AHEI and MDS (i.e., healthier diet) were associated with decreased GrimAA after adjusting for age, sex, body mass index, smoking, physical activity, alcohol consumption, and energy intake ( P < 0.001). We observed that the association of diet quality with GrimAA was stronger in ever-smokers (i.e., former and current smokers) compared to that in never-smokers ( P interaction < 0.001 for both scores). In ever-smokers, adjusted mean Grim AA was 3.95 years (95%CI: 3.47, 4.43) and 0.65 years (95%CI: 0.11, 1.19) in the lowest and highest AHEI quartile category, respectively, or GrimAA was reduced by 1.15 years (95%CI: 0.82, 1.48) per standard deviation (SD) increase in AHEI, P < 0.001. In never-smokers, adjusted mean GrimAA was -1.73 years (95%CI: -2.19, -1.26) and -2.37 years (95%CI: -2.80, 1.94) in the lowest and highest AHEI quartile category, respectively, or GrimAA was reduced by 0.23 years (95%CI: 0.05, 0.40) per SD increase in AHEI, P = 0.01. Similarly, for one SD increase in MDS, the GrimAA was reduced by 0.92 years (95%CI: 0.56, 1.27; P < 0.001) in ever-smokers, but by 0.19 years (95%CI: 0.01, 0.38; P = 0.04) in never-smokers. GrimAA significantly mediated the association between diet quality and all-cause mortality with the mean proportion of 37.0% for AHEI ( P mediation < 0.001) and 25.5% for MDS ( P mediation = 0.001). The mediation effect of GrimAA was more prominent in ever-smokers, which was twice the proportion found in never-smokers for both AHEI and MDS. In conclusion, higher diet quality is associated with decelerated epigenetic aging, which partially explains the beneficial relation of diet quality and healthy lifespan. These results also suggest that better diet quality could be more beneficial in ever-smokers.