Objective To quantify the effectiveness of diet interventions by systematic review of the long-term effects of energy restricted diets in individuals with overweight and obesity. Methods A systematic literature search was conducted for all clinical trials studying the effect of energy restricted diets on body weight in individuals with a BMI>25 kg/m2 with a follow-up of at least 3 years and a minimum of 50 participants. Weight change from baseline and rates of loss to follow-up at the longest follow-up were extracted and analyzed using random-effects models. Results Weighted mean weight loss after 3 years follow-up was 3.5% (95% CI 0.2-6.8%) (n = 6,163) and after 4 years follow-up 4.5% (95% CI 4.3-4.8%) (n = 5,696). Energy restricted diets (n = 1,433) resulted in an average 2.9% (95% CI -3.8 to -2.1%) greater weight loss compared to untreated control groups (n = 1,361). Weight regain was observed in the majority of individuals in all studies. Interpretation of the data is limited by high rates of loss to follow-up and lack of truly untreated control groups. Conclusions On average, the long-term effect of diets on body weight in individuals with obesity is modest, and the response is highly heterogeneous.