Rehabilitation for total knee replacement (TKA) often involves in-person therapy sessions, which can be time consuming and costly. Digital rehabilitation has the potential to address these limitations, but most of these systems offer standardized protocols without considering the patient’s pain, participation, and speed of recovery. Furthermore, most digital systems lack human support in case of need. The aim of this study was to investigate the engagement, safety, and clinical effectiveness of a personalized and adaptative app-based human-supported digital monitoring and rehabilitation program. In this prospective multi-center longitudinal cohort study, 127 patients were included. Undesired events were managed through a smart alert system. Doctors were triggered when there was a suspicion of problems. The drop-out rate, complications and readmissions, PROMS, and satisfaction were collected through the app. There was only 2% readmission. Doctor actions through the platform potentially avoided 57 consultations (85% of alerts). The adherence to the program was 77%, and 89% of the patients would recommend the use of the program. Personalized human-backed-up digital solutions can help to improve the rehabilitation journey of patients after TKA, lower healthcare-related costs by lowering the complication and readmission rate, and improve patient reported outcomes.