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 high-protein 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.