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Objective There is little guidance on return to daily life activities, including work and sport, after a knee replacement surgery. Personalized eHealth programs could provide perioperative guidance to patients, facilitating recovery. We evaluated whether personalized eHealth care enhances return to daily life activities compared to usual care among working-age patients receiving a knee-replacement surgery in The Netherlands.Material and Methods We conducted the multi-centre randomized controlled ACTIVE trial in eleven medical centres across The Netherlands. Patients were included if they were from working age, on the waiting list for knee-replacement surgery, employed 8 hours/week, and willing to return to work. Patients were randomized the either the usual care group or a group receiving an eHealth care program in addition to usual care. The program included an eHealth application with activity tracker, goal attainment scaling and a one-time case-manager consultation. The primary outcome was time from surgery to return to six out of eight self-selected daily life activities, using the PROMIS-Physical Functioning questionnaire. Kaplan-Meier curves and multi-level Cox proportional hazard modelling were used for analyses.Results We randomized 145 patients in the intervention group (54% female, mean age 58 years) and 142 in the control group (51% female, mean age 59 years). Median time to resume self-selected daily life activities was 52 days (IQR 32–84) in the intervention group and 75 days (IQR 36-137) in the usual care group (HR 1.6, 95%CI 1.3–2.0).Conclusion The personalized eHealth care program reduced time to return to self-selected daily life activities by 23 days compared to usual care. Given the worldwide rising prevalence of knee osteoarthritis, especially among working-age patients, this intervention could enhance perioperative care to support personalized medicine.