BACKGROUND: WHO stresses the need to act on the social determinants of tuberculosis. We tested whether alternative social protection programmes have affected tuberculosis case notifications, prevalence, and mortality, and case detection and treatment success rates in 21 European countries from 1995 to 2012. METHODS: We obtained tuberculosis case notification data from the European Centre for Disease Prevention and Control's 2014 European Surveillance System database. We also obtained data for case detection, treatment success, prevalence, and mortality rates from WHO's 2014 tuberculosis database. We extracted data for 21 countries between Jan 1, 1995, and Dec 31, 2012. Social protection data were from EuroStat, 2014 edition. We used multivariate cross-national statistical models to quantify the association of differing types of social protection programmes with tuberculosis outcomes. All analyses were prespecified. FINDINGS: After we controlled for economic output, public health spending, and country fixed effects, each US$100 increase in social protection spending was associated with a decrease per 100,000 population in the number of tuberculosis case notifications of -1·53% (95% CI -0·28 to -2·79; p=0·0191), estimated incidence rates of -1·70% (-0·30 to -3·11; p=0·0201), non-HIV-related tuberculosis mortality rate of -2·74% (-0·66 to -4·82; p=0·0125), and all-cause tuberculosis mortality rate of -3·08% (-0·73 to -5·43; p=0·0127). We noted no relation between increased social spending and tuberculosis prevalence (-1·50% [-3·10 to 0·10] per increase of $100; p=0·0639) or smear-positive treatment success rates (-0·079% [-0·18 to 0·34] per increase of $100; p=0·5235) or case detection (-0·59% [-1·31 to 0·14] per increase of $100; p=0·1066). Old age pension expenditure seemed to have the strongest association with reductions in tuberculosis case notification rates for those aged 65 years or older (-3·87% [-0·95 to -6·78]; p=0·0137). INTERPRETATION: Investment in social protection programmes are likely to provide an effective complement to tuberculosis prevention and treatment programmes, especially for vulnerable groups. FUNDING: European Centre for Disease Prevention and Control.