Patients with cardiometabolic disease are at higher risk for obesity-related adverse effects. Even without weight loss, weight maintenance may be beneficial. We performed a systematic review to identify the effect of nonweight loss-focused lifestyle interventions in adults with cardiometabolic disease. We searched MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials to identify comparative studies of lifestyle interventions (self-management, diet, exercise, or their combination) without a weight loss focus in adults with or at risk for diabetes and cardiovascular disease. Weight, BMI, and waist circumference at ≥12 months were the primary outcomes. Of 24,870 citations, we included 12 trials (self-management, n = 2; diet, n = 2; exercise, n = 2; combination, n = 6) studying 4,206 participants. Self-management plus physical activity ± diet versus minimal/no intervention avoided meaningful weight (-0.65 to -1.3 kg) and BMI (-0.4 to -0.7 kg/m(2)) increases. Self-management and/or physical activity prevented meaningful waist circumference increases versus control (-2 to -4 cm). In patients with cardiometabolic disease, self-management plus exercise may prevent weight and BMI increases and self-management and/or exercise may prevent waist circumference increases versus minimal/no intervention. Future studies should confirm these findings and evaluate additional risk factors and clinical outcomes.