Background Commercially acquired wearable activity trackers such as the Fitbit provide objective, accurate measurements of physically active time and step counts, but it is unclear whether these measurements are more clinically meaningful than self-reported physical activity. Objective The aim of this study was to compare self-reported physical activity to Fitbit-measured step counts and then determine which is a stronger predictor of BMI by using data collected over the same period reflecting comparable physical activities. Methods We performed a cross-sectional analysis of data collected by the Health eHeart Study, a large mobile health study of cardiovascular health and disease. Adults who linked commercially acquired Fitbits used in free-living conditions with the Health eHeart Study and completed an International Physical Activity Questionnaire (IPAQ) between 2013 and 2019 were enrolled (N=1498). Fitbit step counts were used to quantify time by activity intensity in a manner comparable to the IPAQ classifications of total active time and time spent being sedentary, walking, or doing moderate activities or vigorous activities. Fitbit steps per day were computed as a measure of the overall activity for exploratory comparisons with IPAQ-measured overall activity (metabolic equivalent of task [MET]-h/wk). Measurements of physical activity were directly compared by Spearman rank correlation. Strengths of associations with BMI for Fitbit versus IPAQ measurements were compared using multivariable robust regression in the subset of participants with BMI and covariates measured. Results Correlations between synchronous paired measurements from Fitbits and the IPAQ ranged in strength from weak to moderate (0.09-0.48). In the subset with BMI and covariates measured (n=586), Fitbit-derived predictors were generally stronger predictors of BMI than self-reported predictors. For example, an additional hour of Fitbit-measured vigorous activity per week was associated with nearly a full point reduction in BMI (–0.84 kg/m2, 95% CI –1.35 to –0.32) in adjusted analyses, whereas the association between self-reported vigorous activity measured by IPAQ and BMI was substantially smaller in magnitude (–0.17 kg/m2, 95% CI –0.34 to –0.00; P<.001 versus Fitbit) and was dominated by the Fitbit-derived predictor when compared head-to-head in a single adjusted multivariable model. Similar patterns of associations with BMI, with Fitbit dominating self-report, were seen for moderate activity and total active time and in comparisons between overall Fitbit steps per day and IPAQ MET-h/wk on standardized scales. Conclusions Fitbit-measured physical activity was more strongly associated with BMI than self-reported physical activity, particularly for moderate activity, vigorous activity, and summary measures of total activity. Consumer-marketed wearable activity trackers such as the Fitbit may be useful for measuring health-relevant physical activity in clinical practice and research.