BACKGROUND: Behavior change methods involving new ambulatory technologies may improve lifestyle and cardiovascular disease outcomes. OBJECTIVE: This study aimed to provide proof-of-concept analyses of an intervention aiming to increase (1) behavioral flexibility, (2) lifestyle change, and (3) quality of life. The feasibility and patient acceptance of the intervention were also evaluated. METHODS: Patients with cardiovascular disease (N=149; mean age 63.57, SD 8.30 years; 50/149, 33.5% women) were recruited in the Do Cardiac Health Advanced New Generation Ecosystem (Do CHANGE) trial and randomized to the Do CHANGE intervention or care as usual (CAU). The intervention involved a 3-month behavioral program in combination with ecological momentary assessment and intervention technologies. RESULTS: The intervention was perceived to be feasible and useful. A significant increase in lifestyle scores over time was found for both groups (F2,146.6=9.99; P<.001), which was similar for CAU and the intervention group (F1,149.9=0.09; P=.77). Quality of life improved more in the intervention group (mean 1.11, SD 0.11) than CAU (mean -1.47, SD 0.11) immediately following the intervention (3 months), but this benefit was not sustained at the 6-month follow-up (interaction: P=.02). No significant treatment effects were observed for behavioral flexibility (F1,149.0=0.48; P=.07). CONCLUSIONS: The Do CHANGE 1 intervention was perceived as useful and easy to use. However, no long-term treatment effects were found on the outcome measures. More research is warranted to examine which components of behavioral interventions are effective in producing long-term behavior change. TRIAL REGISTRATION: ClinicalTrials.gov NCT02946281; https://www.clinicaltrials.gov/ct2/show/NCT02946281.