INTRODUCTION: Recent research has postulated increased cardiovascular mortality for astronauts who participated in the Apollo lunar missions. The conclusions, however, are based on small numbers of astronauts, are derived from methods with known weaknesses, and are not consistent with prior research.METHODS: Records for NASA astronauts and U.S. Air Force astronauts were analyzed to produce standardized mortality ratios. Lunar astronauts were compared to astronauts who have never flown in space (nonflight astronauts), those who have only flown missions in low Earth orbit (LEO astronauts), and the U.S. general population.RESULTS: Lunar astronauts were significantly older at cohort entry than other astronaut group and lunar astronauts alive as of the end of 2015 were significantly older than nonflight astronauts and LEO astronauts. No significant differences in cardiovascular disease (CVD) mortality rates between astronaut groups was observed, though lunar astronauts were noted to be at significantly lower risk of death by CVD than are members of the U.S. general population (SMR = 13, 95% CI = 3–39).DISCUSSION: The differences in age structure between lunar and nonlunar astronauts and the deaths of LEO astronauts from external causes at young ages lead to confounding in proportional mortality studies of astronauts. When age and follow-up time are properly taken into account using cohort-based methods, no significant difference in CVD mortality rates is observed. Care should be taken to select the correct study design, outcome definition, exposure classification, and analysis when answering questions involving rare occupational exposures.Reynolds RJ, Day SM. Mortality due to cardiovascular disease among Apollo lunar astronauts. Aerosp Med Hum Perform. 2017; 88(5):492–496.