Background: In the WHI DM randomized trial, randomization to the dietary intervention group was associated with a 21% lower breast cancer mortality (P = 0.02) (JCO 2020), and while not an intervention target, with higher physical activity as well. Therefore, we examined whether these lifestyle changes attenuate age-related physical functioning decline. Methods: From 1993-1998, 48,835 postmenopausal women, aged 50-79 years, were randomized to dietary intervention or usual diet comparison groups through 8 years intervention and 19 years cumulative follow-up. Breast cancer findings, as primary outcome, have been reported. Physical functioning was assessed using the RAND 36-Item Short Form Health Survey (SF-36), which assessed limitations of 10 hierarchical physical activities, scored from 0 to 100, with a higher score indicating less limited physical function. The trajectory of longitudinal physical functioning was the primary study outcome, assessed by comparing findings in the two randomization groups, overall, and by baseline physical activity and age decade. Additionally, findings were reported against a disability threshold (when assistance in daily activities is required). Results: Physical functioning was assessed nearly half a million times during the study (n = 495,317) with 11.0 (median) assessments per participant. Physical functioning score was significantly better in the intervention versus comparison groups during the 8-year intervention and extended follow-up through 12 years (median) (P = 0.001), representing a reduction in age-related functional decline. The intervention effect subsequently lost significance at 19 years and both randomization groups crossed the disability threshold at similar times. Differences between randomization groups in physical functioning emerged after stratification by physical activity and age decade (P-interaction = 0.007). Among all participants physically active at entry, the intervention initially had a statistically significant, favorable influence on physical functioning which attenuated post-intervention. In contrast, among younger, physically inactive women 50-59 years of age, the intervention had a persistent, statistically significant, favorable influence on physical functioning with associated delay in crossing the disability threshold. Conclusions: In the primary prevention setting of the WHI DM randomized trial, with long-term follow-up, a dietary intervention which has been shown to reduce breast cancer mortality also significantly reduced age-related functional decline through 12 years. Among all participants, the intervention effect was attenuated with longer follow-up. However, reduction in age-related functional decline was sustained in younger women in the intervention group who were inactive at entry, a potential target population for future behavior interventions. Clinical trial information: NCT00000611.