Background: An infrequently studied question is how the objective measurement of neighborhood walkability modulates physical activity changes during a physical activity intervention program in older adults. We assessed the influence of objectively assessed neighborhood walkability inside the city limits of Palma de Mallorca on the change in physical activity during the intervention program used in the ongoing PREvención con DIeta MEDiterránea (PREDIMED)-Plus trial, a multicenter randomized trial primarily designed to evaluate the long-term impact of an intensive lifestyle intervention on cardiovascular events. Method: The present study involved 228 PREDIMED-Plus senior participants aged between 55 to 75, recruited in Palma de Mallorca (Spain). Overweight/obese adults with the metabolic syndrome were randomized to an intensive weight-loss lifestyle intervention or a control group. A walkability index was calculated within 1 km buffers around each participant’ baseline home address. Physical activity was assessed using the validated REGICOR Short Physical Activity Questionnaire and accelerometer, at baseline and at 2 follow-up visits (six-months and one-year later). Generalised Additive Mixed Models (GAMMs) were fitted to estimate the association between the neighborhood walkability index and changes in physical activity during follow-up in both the intervention and control group. Results: After one-year of intervention, higher neighborhood walkability (1 z-score increment) was positively and significantly associated with moderate-to-vigorous accelerometer assessed physical activity duration, (ß = 3,44; 95% CI = 0.52;6.36 minutes per day). When analyses were stratified by intervention arm, the association was only significant in the intervention group (ß = 6.357; 95% CI = 2.07;10.64 minutes per day) (p for interaction = 0.055). There were no statistically significant associations between neighborhood walkability and self-reported leisure-time physical activity nor brisk walking duration. Conclusions: The results indicate that the walkability of the neighborhood could support a physical activity intervention, helping to maintain or increase older adults’ physical activity.