BACKGROUND: Prostate cancer is a common form of cancer that is often treated with radical prostatectomy, which can leave patients with urinary incontinence and sexual dysfunction. Self-care (pelvic floor muscle exercises and physical activity) is recommended to reduce the side effects. As more and more men are living in the aftermath of treatment, effective rehabilitation support is warranted. Digital self-care support has the potential to improve patient outcomes, but it has rarely been evaluated longitudinally in randomized controlled trials. Therefore, we developed and evaluated the effects of digital self-care support (electronic Patient Activation in Treatment at Home [ePATH]) on prostate-specific symptoms. OBJECTIVE: This study aimed to investigate the effects of web-based and mobile self-care support on urinary continence, sexual function, and self-care, compared with standard care, at 1, 3, 6, and 12 months after radical prostatectomy. METHODS: A multicenter randomized controlled trial with 2 study arms was conducted, with the longitudinal effects of additional digital self-care support (ePATH) compared with those of standard care alone. ePATH was designed based on the self-determination theory to strengthen patients' activation in self-care through nurse-assisted individualized modules. Men planned for radical prostatectomy at 3 county hospitals in southern Sweden were included offline and randomly assigned to the intervention or control group. The effects of ePATH were evaluated for 1 year after surgery using self-assessed questionnaires. Linear mixed models and ordinal regression analyses were performed. RESULTS: This study included 170 men (85 in each group) from January 2018 to December 2019. The participants in the intervention and control groups did not differ in their demographic characteristics. In the intervention group, 64% (53/83) of the participants used ePATH, but the use declined over time. The linear mixed model showed no substantial differences between the groups in urinary continence (β=-5.60; P=.09; 95% CI -12.15 to -0.96) or sexual function (β=-.12; P=.97; 95% CI -7.05 to -6.81). Participants in the intervention and control groups did not differ in physical activity (odds ratio 1.16, 95% CI 0.71-1.89; P=.57) or pelvic floor muscle exercises (odds ratio 1.51, 95% CI 0.86-2.66; P=.15). CONCLUSIONS: ePATH did not affect postoperative side effects or self-care but reflected how this support may work in typical clinical conditions. To complement standard rehabilitation, digital self-care support must be adapted to the context and individual preferences for use and effect. TRIAL REGISTRATION: ISRCTN Registry ISRCTN18055968; https://www.isrctn.com/ISRCTN18055968. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/11625.