Objective To examine the relationship between objectively-assessed moderate-to-vigorous intensity physical activity (MVPA) and 4-year weight loss (WL) and WL maintenance among individuals with diabetes enrolled in the Look AHEAD trial. Methods MVPA was measured on a subgroup of lifestyle intervention participants with accelerometry data at baseline, 1 and 4 years (n=553; age: 59.7±6.8yrs; BMI:35.5±5.9kg/m2). Minutes/week of bout-related MVPA was calculated (≥3 METs, ≥10-min bouts) and adherence to the national PA recommendation for WL maintenance (≥250 min/week) was assessed. Results Independent of 1-year WL, 4-year MVPA (β=-0.003, SE=0.002, p=0.006), but not 1-year MVPA (β=0.0001, SE=0.001, p=0.50) was significantly associated with 4-year WL. Compared to ‘Non-maintainers’ (≥10% WL at Year 1, but