Key PointsQuestionIs a healthy lifestyle more important for lowering the risk of obesity-related disease than obesity itself?FindingsIn this cohort study of 438 583 UK Biobank participants, adults with obesity were at a higher risk of various diseases compared with those who maintained a healthy body weight and lifestyle. For individuals with obesity, engaging in regular exercise, refraining from smoking, consuming alcohol in moderation or not at all, and eating a healthy diet were associated with a decreased risk of cardiovascular disease, kidney failure, gout, sleep disorders, and mood disorders.MeaningThese findings suggest that although adherence to a healthy lifestyle is associated with a reduced risk of several adverse health outcomes in adults with obesity, it does not entirely eradicate the risk of obesity-related diseases.