The rationale for the use of high-protein diets is that they offer a higher level of satiety for a longer period of time when compared with carbohydrates or fats; this diminishes calorie consumption in the long-run. The purpose of this review was to assess the efficacy of long-term randomized clinical trials. We used Pubmed, EBSCO and SCIELO to conduct our searches. Inclusion criteria were: randomized clinical trials conducted in adults, with an intervention/follow-up of at least 24 weeks, stating the specific amount of energy protein (in percentages) in the diet; with a control group with either a conventional energy restricted diet or a high-fat/high-carbohydrate diet, also the studies should provide at least body weight or body mass index (BMI) at the beginning and at the end of the intervention. A total of 481 studies were found. Eight studies met the inclusion criteria. Weight loss difference in those with the highest weight loss with the highprotein diet ranged from 3.7 kg in a six month trial to 1.2 kg in a 17 month trial. The average weight loss of the eight studies in the high-protein diet was 6.3 kg and in the standard diet was 5.0 kg. Although half of the studies showed a higher weight loss with a high-protein diet, three out of four studies with the longest intervention show no statistical difference in weight loss. In this systematic review it was observed that the long-term effect of high-protein diets is neither consistent nor conclusive.