Background <p>This study aimed to evaluate the impact of a cloud-based follow-up exercise prescription on knee function and quality of life in patients undergoing home-based rehabilitation following total knee arthroplasty (TKA), thereby informing the application of telemedicine in post-TKA home rehabilitation.</p> Methods <p>A randomized controlled trial was conducted from February 2023 to January 2024. Patients were divided into a control group and an intervention group according to a random number table. Both groups performed rehabilitation exercises based on exercise prescriptions. After discharge, the control group received follow-up via conventional methods, while the intervention group was monitored using a cloud-based follow-up system. Independent samples t-tests were employed to compare the two patient cohorts with respect to knee function, quality of life, adherence to rehabilitation exercises, and total follow-up costs.</p> Results <p>Of the 164 patients initially enrolled, 151 completed the 12-week follow-up and functional exercises: 75 in the control group and 76 in the intervention group. At 2 and 4 weeks post-surgery, the intervention group demonstrated superior knee function and adherence to rehabilitation exercises compared to the control group (all <i>P</i> &lt; 0.05). At 4 weeks post-surgery, the intervention group also exhibited a higher quality of life (<i>P</i> &lt; 0.05). At 12 weeks post-surgery, no significant differences were observed between the two groups in knee function, quality of life, or adherence to rehabilitation exercises. The total follow-up cost for the intervention group was lower than that of the control group (<i>p</i> &lt; 0.05).</p> Conclusions <p>Cloud-based follow-up exercise prescriptions can improve knee function and quality of life in home-based patients in the early stages (within 4 weeks) of rehabilitation exercises after TKA, which is of clinical significance.</p> Trial registration <p>ChiCTR2200067031, registered 23 December 2022, <a href="https://www.chictr.org.cn/bin/project/edit?pid=185737">https://www.chictr.org.cn/bin/project/edit?pid=185737</a>.</p>