The aim of this study was to investigate whether changes in waist circumference were associated with mortality and to evaluate the effect of concurrent changes in body mass index (BMI) on this relationship. Data on 26,625 healthy men and women from the Danish Diet, Cancer and Health study were analyzed. Over 6.7 years of follow-up, 568 and 361 deaths occurred among men and women, respectively. Results showed that changes in waist circumference were positively associated with mortality, whereas changes in BMI were inversely associated with mortality. Moreover, the positive association with changes in waist circumference was stronger after adjustment for concurrent changes in BMI, and the inverse association with changes in BMI was stronger after the adjustment for concurrent changes in waist circumference. Thus, these results emphasize the need to measure both waist and BMI in assessing mortality risk.