For decades, researchers have noted systematic shifts in cause-of-death patterns as mortality levels change. The notion of the “epidemiologic transition” has influenced thinking about the evolution of health in different societies and the response of the health system to these changes. This article re-examines the epidemiologic transition in terms of empirical regularities in the cause composition of mortality by age and sex since 1950, and considers whether the theory of epidemiologic transition presents a durable framework for understanding more recent patterns. Age-sex-specific mortality rates from three broad cause groups are analyzed: Group 1 (communicable diseases, maternal and perinatal causes, and nutritional deficiencies); Group 2 (noncommunicable diseases); and Group 3 (injuries), using the most extensive international database on mortality by cause, including 1,576 country-years of observation, and new statistical models for compositional data. The analyses relate changes in cause-of-death patterns to changing levels of all-cause mortality and income per capita. The results confirm that declines in overall mortality are accompanied by systematic changes in the composition of causes in many age groups. These changes are most pronounced among children, for whom Group 1 causes decline as overall mortality falls, and in younger adults, where strikingly different patterns are found for men (shift from Group 3 to Group 2) compared to women (shift toward Group 2 then Group 3). The underlying patterns that emerge from this analysis offer insights into the epidemiologic transition from high-mortality to low-mortality settings.