In the past, interventions aimed at reducing obesity have mainly targeted at weight loss treatment in obese adults, with limited long-term effects. With the increasing number of people being obese and being at risk for obesity, there has been a shift in focus towards prevention of obesity. We conducted a systematic review of the peer-reviewed literature on the efficacy of obesity prevention interventions in adults in order to identify effective interventions and intervention elements. Pubmed, OVID, and Web of Science databases were searched from January 1996 to June 2006. Interventions aimed at primary prevention of weight gain among adults achieved by focusing on dietary intake, physical activity or the combination of both were included. The outcome measure had to be difference in change in body mass index or body weight between the intervention and the control groups. Nine studies were included, five long-term studies (at least 1 year) and four short-term (3 months to 1 year). Seven studies evaluated an intervention that focused on a combination of diet and physical activity to prevent weight gain, one on diet only and one on physical activity only. One dietary intervention (long-term), and three combined dietary and physical activity interventions (one long-term and two short-term) produced significantly positive results at end of follow-up. The two long-term, effective interventions consisted of intensive and long-term intervention implementation, including groups sessions designed to promote behavioural changes. The current evidence of efficacy of obesity prevention interventions is based on a very small number of studies. Some studies showed a positive impact on body mass index or weight status, but there was too much heterogeneity in terms of study design, theoretical underpinning and target population to draw firm conclusions about which intervention approaches are more effective than others. More research is urgently needed to extend the body of evidence.