© 2014 American College of Physicians. Background: Many smartphone applications (apps) for weight loss are available, but little is known about their effectiveness. Objective: To evaluate the effect of introducing primary care patients to a free smartphone app for weight loss.Design: Randomized, controlled trial. (ClinicalTrials.gov: NCT01650337).Setting: 2 academic primary care clinics.Patients: 212 primary care patients with body mass index of 25 kg/m2 or greater. Intervention: 6 months of usual care without (n = 107) or with (n = 105) assistance in downloading the MyFitnessPal app (MyFitnessPal).Measurements: Weight loss at 6 months (primary outcome) and changes in systolic blood pressure and behaviors, frequency of app use, and satisfaction (secondary outcomes).Results: After 6 months, weight change was minimal, with no difference between groups (mean between-group difference, -0.30 kg [95% CI, -1.50 to 0.95 kg]; P = 0.63). Change in systolic blood pressure also did not differ between groups (mean between-group difference, -1.7 mm Hg [CI, -7.1 to 3.8 mm Hg]; P = 0.55). Compared with patients in the control group, those in the intervention group increased use of a personal calorie goal (mean between-group difference, 2.0 d/wk [CI, 1.1 to 2.9 d/wk]; P < 0.001), although other self-reported behaviors did not differ between groups. Most users reported high satisfaction with MyFitnessPal, but logins decreased sharply after the first month.Limitations: Despite being blinded to the name of the app, 14 control group participants (13%) used MyFitnessPal. In addition, 32% of intervention group participants and 19% of control group participants were lost to follow-up at 6 months. The app was given to patients by research assistants, not by physicians.Conclusion: Smartphone apps for weight loss may be useful for persons who are ready to self-monitor calories, but introducing a smartphone app is unlikely to produce substantial weight change for most patients.Primary Funding Source: Robert Wood Johnson Foundation Clinical Scholars Program, National Institutes of Health/National Center for Advancing Translational Sciences for the UCLA Clinical and Translational Science Institute, and the Resource Centers for Minority Aging Research Center for Health Improvement of Minority Elderly under the National Institutes of Health/National Institute on Aging. Ann Int.