Background: Enhancing individual’s health literacy for weight loss is important in addressing the increasing burden of chronic disease due to overweight and obesity. We conducted a systematic review and narrative synthesis to determine the effectiveness of lifestyle interventions aimed at improving adults’ knowledge and skills for weight loss in primary health care. The literature search included English-language papers published between 1990 and 30 June 2013 reporting research conducted within Organisation for Economic Cooperation and Development member countries. Twelve electronic databases and five journals were searched and this was supplemented by hand searching. The study population included adults (≥18 years old) with a body mass index (BMI) ≥25 kg/m2 and without chronic disease at baseline. We included intervention studies with a minimum 6 month follow-up. Three reviewers independently extracted data and two reviewers independently assessed study quality by using predefined criteria. The main outcome was a change in measured weight and/or BMI over 6 or 12 months. Results: Thirteen intervention studies, all targeting diet, physical activity and behaviour change to improve individuals’ knowledge and/or skills for weight loss, were included with 2,089 participants. Most (9/13) of these studies were of a ‘weak’ quality. Seven studies provided training to the intervention deliverers. The majority of the studies (11/13) showed significant reduction in weight and/or BMI in at least one follow-up visit. There were no consistent associations in outcomes related to the mode of intervention delivery, the number or type of providers involved or the intensity of the intervention. Conclusions: There was evidence for the effectiveness of interventions that focussed on improving knowledge and skills (health literacy) for weight loss. However, there was insufficient evidence to determine relative effectiveness of individual interventions. The lack of studies measuring socio-economic status needs to be addressed in future research as the rates of obesity are high in disadvantaged population groups. ; Nighat Faruqi, Catherine Spooner, Chandni Joshi, Jane Lloyd, Sarah Dennis, Nigel Stocks, Jane Taggart, and Mark F Harris