Due to the positive effects of rehabilitation declining over time, the aim of this study was to investigate the long-term physical activity level (PAL) following inpatient rehabilitation in relation to the use of a smartphone-based after-care program. 202 patients (mean Body Mass Index (BMI): 30,8 kg/m2; 61% female) with chronic diseases (e.g., diabetes mellitus, obesity, chronic low back pain, depression) were recruited between 08/2020 and 08/2021 in this single-arm observational study. All patients underwent a 3-week inpatient rehabilitation program. PAL (in total activity minutes/week) was measured with a validated (online) questionnaire (Freiburger Questionnaire on PA) after 3, 6, 9, and 12 months. App usage (online time, completion of a course) was recorded automatically and used to evaluate the app user behavior (adherence). A variety of socio-economic factors (age, sex, education level, income etc.) were collected to identify possible barriers of app use. Except for sex, no significant difference was observed for socio-economic factors regarding app usage behavior. Median PAL significantly increased after rehabilitation in the total cohort from 360 min/week (before rehabilitation) to 460 min/week 6 months after rehabilitation, then declined to 420 min/week 9 months after rehabilitation before falling below baseline level after 12 months. There was no significant difference in PAL between app users (45%, 91/202) and non-users (55%, 111/202), although app users tended to retain higher activity levels after 3 and 6 months, respectively. Overall, our study emphasizes the effectiveness of a 3-week rehabilitation program on PAL and the acceptance and usability of a smartphone-based after-care program in this patient group. The adherence to this 3-months after-care app program was acceptable (30%), with modest evidence supporting the effectiveness of app use to sustain PAL in the short term.