BackgroundWeb-based aftercare can help to stabilize treatment effects and support transition after inpatient treatment, yet uptake by patients seems limited in routine care and little is known about the mechanisms of adoption and implementation.ObjectiveThe aim of this study was to (1) determine acceptance of Web-based aftercare and (2) explore its drivers and barriers in different subgroups of a mixed inpatient sample.MethodIn a cross-sectional design, 38.3% (374/977) of the inpatients from a broad spectrum of diagnostic groups (psychosomatic, cardiologic, orthopedic, pediatric, and substance-related disorders) filled out a self-administered questionnaire prior to discharge. Drivers and barriers to patients’ acceptance of Web-based aftercare were examined based on an extension to the “unified theory of acceptance and use of technology” (UTAUT). In total, 16.7% (59/353) of the participants indicated prior use of eHealth interventions.ResultsAcceptance (min 1, max 5) was low (mean 2.56, SD 1.22) and differed between diagnostic groups (Welch F4,133.10 =7.77, P<.001), with highest acceptance in adolescent patients (mean 3.46, SD 1.42). Acceptance was significantly predicted by 3 UTAUT predictors: social influence (beta=.39, P<.001), performance expectancy (beta=.31, P<.001), and effort expectancy (beta=.22, P<.001). Furthermore, stress due to permanent availability (beta=−.09, P=.01) was negatively associated with acceptance.ConclusionThis study demonstrated a limited acceptance of Web-based aftercare in inpatients. Expectations, social environment’s attitude, and negative experience with permanent availability influence eHealth acceptance. Improving implementation, therefore, means increasing eHealth experience and literacy and facilitating positive attitudes in patients and health professionals through education and reduction of misconceptions about effectiveness or usability.