Abstract Background By 2030, the number of US adults age ≥65 will exceed 70 million. Their quality of life has been declared a national priority by the US government. Objective Assess effects of an eHealth intervention for older adults on quality of life, independence, and related outcomes. Design Multi-site, 2-arm (1:1), non-blinded randomized clinical trial. Recruitment November 2013 to May 2015; data collection through November 2016. Setting Three Wisconsin communities (urban, suburban, and rural). Participants Purposive community-based sample, 390 adults age ≥65 with health challenges. Exclusions: long-term care, inability to get out of bed/chair unassisted. Intervention Access (vs. no access) to interactive website (ElderTree) designed to improve quality of life, social connection, and independence. Measures Primary outcome: quality of life (PROMIS Global Health). Secondary: independence (Instrumental Activities of Daily Living); social support (MOS Social Support); depression (Patient Health Questionnaire-8); falls prevention (Falls Behavioral Scale). Moderation: healthcare use (Medical Services Utilization). Both groups completed all measures at baseline, 6, and 12 months. Results Three hundred ten participants (79%) completed the 12-month survey. There were no main effects of ElderTree over time. Moderation analyses indicated that among participants with high primary care use, ElderTree (vs. control) led to better trajectories for mental quality of life (OR=0.32, 95% CI 0.10–0.54, P=0.005), social support received (OR=0.17, 95% CI 0.05–0.29, P=0.007), social support provided (OR=0.29, 95% CI 0.13–0.45, P<0.001), and depression (OR= −0.20, 95% CI −0.39 to −0.01, P=0.034). Supplemental analyses suggested ElderTree may be more effective among people with multiple (vs. 0 or 1) chronic conditions. Limitations Once randomized, participants were not blind to the condition; self-reports may be subject to memory bias. Conclusion Interventions like ET may help improve quality of life and socio-emotional outcomes among older adults with more illness burden. Our next study focuses on this population. Trial Registration ClinicalTrials.gov; registration ID number: NCT02128789