Intervention strategies are available for reducing the high global burden of hazardous alcohol use as a risk factor for disease, but little is known about their potential costs and effects at a population level. This study set out to estimate these costs and effects. Analyses were carried out for 12 epidemiological World Health Organization subregions of the world. A population model was used to estimate the impact of evidence-based personal and nonpersonal interventions--including brief physician advice, taxation, roadside random breath testing, restricted sales access and advertising bans. Costs were measured in international dollars (I$); population-level intervention effects were gauged in terms of disability-adjusted life years (DALYs) averted. Average and incremental cost-effectiveness ratios (CERs) were computed. The most costly interventions to implement are brief advice in primary care and roadside breath testing of drivers. In populations with a high prevalence of heavy drinkers (more than 5%, such as Europe and North America), the most effective and cost-effective intervention was taxation (more than 500 DALYs averted per 1 million population; CER < I$500 per DALY averted). In populations with a lower prevalence of heavy drinking, however, taxation is estimated to be less cost effective overall than other, more targeted strategies, such as brief physician advice, roadside breath testing and advertising bans. The most efficient public health response to the burden of alcohol use depends on the prevalence of hazardous alcohol use, which is related to overall per capita consumption. Population-wide measures, such as taxation, are expected to represent the most cost-effective response in populations with moderate or high levels of drinking, whereas more targeted strategies are indicated in populations with lower rates of hazardous alcohol use.