BACKGROUND: As the increasing prevalence of type 2 diabetes mellitus has put pressure on health systems to appropriately manage these patients, there have been a growing number of mobile apps designed to improve the self-management of diabetes. One such app, BlueStar, has been shown to significantly reduce hemoglobin A (HbA) levels in small studies and is the first app in the United States to receive Food and Drug Administration approval as a mobile prescription therapy. However, the impact of the app across real-world population among different clinical sites and health systems remains unclear. OBJECTIVE: The primary objective of this study was to conduct a pragmatic randomized controlled trial of the BlueStar mobile app to determine if app usage leads to improved HbA levels among diverse participants in real-life clinical contexts. We hypothesized that this mobile app would improve self-management and HbA levels compared with controls. METHODS: The study consisted of a multicenter pragmatic randomized controlled trial. Overall, 110 participants randomized to the immediate treatment group (ITG) received the intervention for 6 months, and 113 participants randomized to the wait-list control (WLC) group received usual care for the first 3 months and then received the intervention for 3 months. The primary outcome was glucose control measured by HbA levels at 3 months. Secondary outcomes assessed intervention impact on patient self-management, experience of care, and self-reported health utilization using validated scales, including the Problem Areas in Diabetes, the Summary of Diabetes Self-Care Activities, and the EuroQol-5D. Intervention usage data were collected directly from the app. RESULTS: The results of an analysis of covariance controlling for baseline HbA levels did not show evidence of intervention impact on HbA levels at 3 months (mean difference [ITG-WLC] -0.42, 95% CI -1.05 to 0.21; P=.19). Similarly, there was no intervention effect on secondary outcomes measuring diabetes self-efficacy, quality of life, and health care utilization behaviors. An exploratory analysis of 57 ITG participants investigating the impact of app usage on HbA levels showed that each additional day of app use corresponded with a 0.016-point decrease in participants' 3-month HbA levels (95% CI -0.03 to -0.003). App usage varied significantly by site, as participants from 1 site logged in to the app a median of 36 days over 14 weeks (interquartile range [IQR] 10.5-124); those at another site used the app significantly less (median 9; IQR 6-51). CONCLUSIONS: The results showed no difference between intervention and control arms for the primary clinical outcome of glycemic control measured by HbA levels. Although there was low usage of the app among participants, results indicate contextual factors, particularly site, had a significant impact on overall usage. Future research into the patient and site-specific factors that increase app utilization are needed. TRIAL REGISTRATION: Clinicaltrials.gov NCT02813343; https://clinicaltrials.gov/ct2/show/NCT02813343 (Archived by WebCite at https://clinicaltrials.gov/ct2/show/NCT02813343).