<p>Physical inactivity is the fourth largest cause of global mortality. Health organizations have requested a tool to objectively measure physical activity because many specific and causal relationships between activity and health outcomes are not clearly understood. Existing activity monitors are either unsuitable for large-scale use or have substantial error. We present OpenMetabolics, a biomechanically-informed activity monitor that employs a smartphone in a pants pocket which measures leg motion to estimate energy expenditure. OpenMetabolics uses a data-driven machine learning model to capture the relationship between underlying leg muscle activity and energy expended during common physical activities. OpenMetabolics estimated energy expenditure with 18% cumulative error across all real-world activities, approximately two times lower than existing tools. We developed a pocket motion artifact correction model to accurately monitor energy expenditure when the smartphone is in a pocket of various types of clothing. A week-long, at-home monitoring study highlighted individual and population-level activity patterns across various timescales. We have made the data, code, and smartphone application open source. This accurate and accessible activity monitor could be deployed for large-scale studies with many patient populations to relate activity to health outcomes, inform health policy, and develop interventions.</p>