Background: Countries have agreed to reduce premature mortality (defined as the probability of dying between the ages of 30 years and 70 years) from four main non-communicable diseases (NCDs)--cardiovascular diseases, chronic respiratory diseases, cancers, and diabetes--by 25% from 2010 levels by 2025 (referred to as 25×25 _target). _targets for selected NCD risk factors have also been agreed on. We estimated the contribution of achieving six risk factor _targets towards meeting the 25×25 mortality _target.

Methods: We estimated the impact of achieving the _targets for six risk factors (tobacco and alcohol use, salt intake, obesity, and raised blood pressure and glucose) on NCD mortality between 2010 and 2025. Our methods accounted for multi-causality of NCDs and for the fact that when risk factor exposure increases or decreases, the harmful or beneficial effects on NCDs accumulate gradually. We used data for risk factor and mortality trends from systematic analyses of available country data. Relative risks for the effects of individual and multiple risks, and for change in risk after decreases or increases in exposure, were from re-analyses and meta-analyses of epidemiological studies.

Findings: If risk factor _targets are achieved, the probability of dying from the four main NCDs between the ages of 30 years and 70 years will decrease by 22% in men and by 19% in women between 2010 and 2025, compared with a decrease of 11% in men and 10% in women under the so-called business-as-usual trends (ie, projections based on current trends with no additional action). Achieving the risk factor _targets will delay or prevent more than 37 million deaths (16 million in people aged 30-69 years and 21 million in people aged 70 years or older) from the main NCDs over these 15 years compared with a situation of rising or stagnating risk factor trends. Most of the benefits of achieving the risk factor _targets, including 31 million of the delayed or prevented deaths, will be in low-income and middle-income countries, and will help to reduce the global inequality in premature NCD mortality. A more ambitious _target on tobacco use (a 50% reduction) will almost reach the _target in men (>24% reduction in the probability of death), and enhance the benefits to a 20% reduction in women.

Interpretation: If the agreed risk factor _targets are met, premature mortality from the four main NCDs will decrease to levels that are close to the 25×25 _target, with most of these benefits seen in low-income and middle-income countries. On the basis of mortality benefits and feasibility, a more ambitious _target than currently agreed should be adopted for tobacco use.

Funding: UK MRC.