Background Socioeconomic inequalities are increasingly recognised as an important public health issue, although their role in the leading causes of mortality in urban areas in Europe has not been fully evaluated. In this study, we used data from the INEQ-CITIES study to analyse inequalities in cause-specific mortality in 15 European cities at the beginning of the 21st century. Methods A cross-sectional ecological study was carried out to analyse 9 of the leading specific causes of death in small areas from 15 European cities. Using a hierarchical Bayesian spatial model, we estimated smoothed Standardized Mortality Ratios, relative risks and 95% credible intervals for cause-specific mortality in relation to a socioeconomic deprivation index, separately for men and women. Results We detected spatial socioeconomic inequalities for most causes of mortality studied, although these inequalities differed markedly between cities, being more pronounced in Northern and Central-Eastern Europe. In the majority of cities, most of these causes of death were positively associated with deprivation among men, with the exception of prostatic cancer. Among women, diabetes, ischaemic heart disease, chronic liver diseases and respiratory diseases were also positively associated with deprivation in most cities. Lung cancer mortality was positively associated with deprivation in Northern European cities and in Kosice, but this association was non-existent or even negative in Southern European cities. Finally, breast cancer risk was inversely associated with deprivation in three Southern European cities. Conclusions The results confirm the existence of socioeconomic inequalities in many of the main causes of mortality, and reveal variations in their magnitude between different European cities.