Abstract Objective To identify and summarize rigorous evaluations of psychosocial and educational interventions aimed at the primary prevention of alcohol misuse by young people aged up to 25 years, especially over the longer term (>3 years). Methods Cochrane Collaboration Systematic Review. Data sources A comprehensive search of 22 databases and recursive checking of bibliographies for randomized and non-randomized controlled trials and interrupted time-series studies. Main outcome measures Objective or self-report measures of alcohol use and misuse. Results Fifty-six studies were selected for inclusion in the systematic review. Twenty of the 56 studies showed evidence of ineffectiveness. No firm conclusions about the effectiveness of prevention interventions in the short- and medium term were possible. Over the longer term (>3 years), the Strengthening Families Programme (SFP) showed promise as an effective prevention intervention. The Number Needed to Treat (NNT) for the SFP over 4 years for three alcohol initiation behaviours (alcohol use, alcohol use without permission and first drunkenness) was 9 (for all three behaviours). One study also highlighted the potential value of culturally focused skills training over the longer-term (NNT = 17 over 3.5 years for 4+ drinks in the last week) Conclusions (1) Research into important outcome variables needs to be undertaken; (2) the methodology of evaluations needs to be improved; (3) the SFP needs to be evaluated on a larger scale and in different settings; (4) culturally focused interventions require further development and rigorous evaluation; and (5) an international register of alcohol and drug misuse prevention interventions should be established and criteria agreed for rating prevention interventions in terms of safety, efficacy and effectiveness.