BackgroundMindfulness has become increasingly popular, and positive outcomes have been reported for mindfulness-based interventions (MBIs) in reducing stress. These findings make room for innovative perspectives on how MBIs could be applied, for instance through mobile health (mHealth). ObjectiveThe aim of this study is to investigate whether a nonguided mindfulness mobile app can decrease perceived stress in a nonclinical Dutch population over the course of 8 weeks, with follow-up at 6 months. MethodsA randomized controlled trial was performed to compare an experimental group that made use of a structured 8-week mHealth mindfulness program and a control group after 8 weeks, with follow-up after 6 months. Participants were recruited via a national television program. The primary outcome measure was perceived stress as measured by the Perceived Stress Scale, secondary outcomes were symptoms of burnout (measured using the visual analog scale [VAS]) and psychological symptoms (measured using the Four-Dimensional Symptom Questionnaire [4DSQ] at follow-up). Outcomes were analyzed using a multilevel regression model. ResultsAt baseline, 587 respondents were included. Results showed no postintervention differences between groups for the level of perceived stress. With regard to the secondary outcome measures, the VAS for emotional exhaustion and physical exhaustion showed significantly lower scores for the experimental group after 8 weeks (P=.04 and P=.01, respectively), but not at follow-up. There were no differences between groups for psychological symptoms measured using the 4DSQ. ConclusionsThese findings do not support our hypothesis that using the mindfulness app would reduce stress levels. However, our findings related to diminished exhaustion at 8 weeks are encouraging and require further investigation. Trial RegistrationClinicalTrials.gov NCT05246800; https://clinicaltrials.gov/show/NCT05246800