Key PointsQuestionWhat is the effectiveness of lifestyle intervention among people with severe mental illness compared with treatment as usual?FindingsIn this pragmatic randomized clinical trial including 224 participants, lifestyle intervention in an outpatient treatment setting demonstrated a significant body weight change (−3.3 kg) compared with treatment as usual from baseline to 12 months.MeaningThe lifestyle intervention was effective in reducing weight in people with severe mental illness and may lead to reduced risk of cardiometabolic disorders.