The Diet Quality Index (DQI) was developed to measure overall dietary patterns and to predict chronic disease risk. This study examined associations between DQI and short-term all-cause, all-circulatory-disease, and all-cancer mortality in the American Cancer Society Cancer Prevention Study II Nutrition Cohort, a cohort of US adults aged 50–79 years enrolled in a prospective study. After 4 years of follow-up (1992–1996), there were 869 deaths among 63,109 women and 1,736 deaths among 52,724 men. All study participants reported being disease free at baseline in 1992–1993. In age-adjusted Cox models, a higher DQI, which was indicative of a poorer quality diet, was positively related to all-cause and all-circulatory-disease mortality rates in both women and men and to cancer mortality in men only. However, in fully adjusted Cox models, only circulatory disease mortality was clearly positively related to DQI and only in women (medium-low-quality diet vs. highest-quality diet: rate ratio = 1.86, 95% confidence interval: 1.19, 2.89). Although trend tests indicated significant positive relations between DQI and all-cause mortality, effects were small (rate ratios ≤ 1.31), and confidence intervals were wide, generally including 1.0. DQI was unrelated to cancer mortality. As currently constructed, the DQI may have limited ability to predict mortality.