Objective: This 12-month randomized, non-inferiority clinical trial sought to determine the impact of consuming soy protein as part of an energy-restricted, high-protein diet on weight loss, body composition and cardiometabolic health. Methods: Seventy-one adults (58 female) with overweight or obesity (body mass index: 32.9 ± 3.6 kg m−2) were randomly assigned to consume three servings of soy (S) or non-soy (NS) protein foods per day for 12 months. All participants completed a group-based behavioural weight loss program lasting 4 months (M4), and follow-up assessments were completed at month 12 (M12). Results: Body weight was reduced in both groups at M4 (S: −7.0% ± 5.2%, NS: −7.1% ± 5.7%) and M12 (S: 3.6% ± 5.1%, NS: −4.8% ± 7.3%). Body weight reductions (mean difference [90% confidence interval]) were not different between S and NS at either time point (M4: −0.16% [−1.4, 3.6], P = 0.90; M12: 1.1% [−1.4, 3.6], P = 0.44). Differences in body fat mass loss were not different between S and NS at M4 (0.29 ± 0.84 kg, P = 0.73) or M12 (0.78 ± 1.5 kg, P = 0.59). Weight loss-induced improvements in cholesterol, triglycerides and blood pressure did not differ between S and NS. Conclusion: These results indicate that soy-based protein foods can be effectively incorporated into an energy-restricted, high-protein diet for improving body weight, body composition and cardiometabolic health.