Objective: The objective of this randomized equivalence trial was to determine the impact of consuming lean beef as part of a high protein (HP) weight-reducing diet on changes in body weight, body composition and cardiometabolic health. Methods: A total of 120 adults (99 female) with overweight or obesity (BMI: 35.7 ± 7.0 kg m−2) were randomly assigned to consume either a HP diet with ≥4 weekly servings of lean beef (B; n = 60) or a HP diet restricted in all red meats (NB; n = 60) during a 16-week weight loss intervention. Results: Body weight was reduced by 7.8 ± 5.9% in B and 7.7 ± 5.5% in NB (p < 0.01 for both). Changes in percent body weight were equivalent between B and NB (mean difference: 0.06%, 90% confidence interval: (−1.7, 1.8)). Fat mass was reduced in both groups (p < 0.01; B: 8.0 ± 0.6 kg, NB: 8.6 ± 0.6 kg), while lean mass was not reduced in either group. Improvements in markers of cardiometabolic health (total cholesterol, low-density lipoprotein cholesterol, triglycerides and blood pressure) were not different between B and NB. Conclusion: Results of this study demonstrate that HP diets – either rich or restricted in red meat intakes – are effective for decreasing body weight and improving body composition and cardiometabolic health.