Summary Background Introduced in 2004, the UK's Quality and Outcomes Framework (QOF) is the world's largest primary care pay-for-performance programme. We tested whether the QOF was associated with reduced population mortality. Methods We used population-level mortality statistics between 1994 and 2010 for the UK and other high-income countries that were not exposed to pay-for-performance. The primary outcome was age-adjusted and sex-adjusted mortality per 100 000 people for a composite outcome of chronic disorders that were targeted by the QOF. Secondary outcomes were age-adjusted and sex-adjusted mortality for ischaemic heart disease, cancer, and a composite of all non-targeted conditions. For each study outcome, we created a so-called synthetic UK as a weighted combination of comparison countries. We then estimated difference-in-differences models to test whether mortality fell more in the UK than in the synthetic UK after the QOF. Findings Introduction of the QOF was not significantly associated with changes in population mortality for the composite outcome (−3·68 per 100 000 population 95% CI −8·16 to 0·80; p=0·107), ischaemic heart disease (−2·21 per 100 000 –6·86 to 2·44; p=0·357), cancer (0·28 per 100 000 –0·99 to 1·55; p=0·679), or all non-targeted conditions (11·60 per 100 000 –3·91 to 27·11; p=0·143). Interpretation Although we noted small mortality reductions for a composite outcome of targeted disorders, the QOF was not associated with significant changes in mortality. Our findings have implications for the probable effects of similar programmes on population health outcomes. The relation between incentives and mortality needs to be assessed in specific disease domains. Funding None.