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The objective of this study was to determine the risk for various causes of posttrial death associated with vacation frequency during the Multiple Risk Factor Intervention Trial (MRFIT).Middle-aged men at high risk for coronary heart disease (CHD) were recruited for the MRFIT. As part of the questionnaires administered during the first five annual visits, men were asked whether they had had a vacation during the past year. For trial survivors (N = 12,338), the frequency of these annual vacations during the trial were used in a prospective analysis of posttrial all-cause and cause-specific mortality during the 9-year follow-up period.The relative risk (RR) associated with more annual vacations during the trial was 0.83 (95% confidence interval [CI], 0.71–0.97) for all-cause mortality during the 9-year follow-up period. For cause of death, the RRs were 0.71 (95% CI, 0.58–0.89) and 0.98 (95% CI, 0.78–1.23) for cardiovascular and noncardiovascular causes, respectively. The RR was 0.68 (95% CI, 0.53–0.88) for CHD (including acute myocardial infarction). These associations remained when statistical adjustments were made for possible confounding variables, including baseline characteristics (eg, income), MRFIT group assignment, and occurrence of a nonfatal cardiovascular event during the trial.The frequency of annual vacations by middle-aged men at high risk for CHD is associated with a reduced risk of all-cause mortality and, more specifically, mortality attributed to CHD. Vacationing may be good for your health.