© 2016 American Congress of Rehabilitation Medicine Objectives To evaluate the extent of variability in functional responses in participants in the Lifestyle Interventions and Independence for Elders (LIFE) study and to identify the relative contributions of intervention adherence, physical activity, and demographic and health characteristics to this variability. Design Secondary analysis. Setting Multicenter institutions. Participants A volunteer sample (N=1635) of sedentary men and women aged 70 to 89 years who were able to walk 400m but had physical limitations, defined as a Short Physical Performance Battery (SPPB) score of ≤9. Interventions Moderate-intensity physical activity (n=818) consisting of aerobic, resistance, and flexibility exercises performed both center-based (2times/wk) and home-based (3–4times/wk) sessions or health education program (n=817) consisting of weekly to monthly workshops covering relevant health information. Main Outcome Measures Physical function (gait speed over 400m) and lower extremity function (SPPB score) assessed at baseline and 6, 12, and 24 months. Results Greater baseline physical function (gait speed, SPPB score) was negatively associated with change in gait speed (regression coefficient β=−.185; P<.001) and change in SPPB score (β=−.365; P<.001), whereas higher number of steps per day measured by accelerometry was positively associated with change in gait speed (β=.035; P<.001) and change in SPPB score (β=.525; P<.001). Other baseline factors associated with positive change in gait speed and/or SPPB score include younger age (P<.001), lower body mass index (P<.001), and higher self-reported physical activity (P=.002). Conclusions Several demographic and physical activity–related factors were associated with the extent of change in functional outcomes in participants in the LIFE study. These factors should be considered when designing interventions for improving physical function in older adults with limited mobility.