In the 1990s, Moscow and Saint Petersburg registered similar rates and trends in the standardized mortality coefficient (SMC), which have changed since 1998. Objective — to compare the levels and causes of deaths in Saint Petersburg and Moscow in 2015. Material and methods. The investigation used the data of the Russian Federal State Statistics Service on the average annual size of the population and on the number of deceased people by the causes of death in some-year age groups based on the brief nomenclature of causes of death. The mortality rates were calculated using software based on the European standard. Results. SMS in Saint Petersburg was 20% higher than that in Moscow, with the exception of mortality in children (under 11 years). SMS from diseases was 1.18% higher in Saint Petersburg, that from external causes was 1.32 times greater; and that from causes related to alcohol and drug use was 1.8 times higher. Ten largest SKS-related causes were responsible for 55.1% of deaths in Moscow and for 49.4% in Saint-Petersburg (atherosclerotic heart disease for 14 and 10.6%, respectively). The malignant tumor deaths due to 28 of 29 causes were lower in Moscow. SMS from circulatory system disease was 33% higher in Saint Petersburg; but that from some diseases was higher in Moscow. The differences in 52 of 295 causes of death between the two megalopolises were more than 3-fold higher. Conclusion. The differences in mortality rates may be associated with environmental characteristics, the levels of economic development, healthcare financing, availability of medical care, and other factors. Both cities show a high proportion of deaths due to the causes that have no diagnostic criteria and are not established as a diagnosis in patients. In a number of cases, the differences are likely to be caused by the peculiarities of establishing the cause of death and filling out medical death certificates.