Purpose: Chronic diseases such as cancer and cardiovascular disease (CVD) are well-established causes of disability and premature deaths. Dietary components that are known to affect chronic inflammation have been implicated in the etiology and prognosis of these chronic diseases. We examined the ability of the dietary inflammatory index (DII) to predict overall, cancer and CVD mortality in the Iowa Women’s Health study. Methods: The DII was computed from baseline dietary intake assessed in this cohort of 37,525 women, who were aged 55–69 years when enrolled starting in 1986. During the follow-up period, through December 31, 2010, in a total of 17,793 deaths, 5044 cancer- and 6528 CVD-related deaths were identified through mortality record linkage. Cox proportional hazards regression was used to estimate hazard ratios (HR) with DII expressed both as a continuous variable and as quartiles. Results: Comparing subjects in DII Quartile 4 versus Quartile 1, modest positive associations were noted for all-cause mortality (HRQ4vsQ1 1.07; 95 % CI 1.01–1.13; p-trend = 0.006), digestive cancer mortality (HRQ4vsQ1 1.19; 95 % CI 1.00–1.43; p-trend = 0.05), CVD mortality (HRQ4vsQ1 1.09; 95 % CI 1.01–1.18; p-trend = 0.08), non-cancer/non-CVD/non-acute mortality (HRQ4vsQ1 1.09; 95 % CI 1.00–1.19; p-trend = 0.19), coronary heart disease (CHD) mortality (HRQ4vsQ1 1.17; 95 % CI 1.05–1.30; p-trend = 0.001) and chronic obstructive pulmonary disease (COPD) mortality (HRQ4vsQ1 1.43; 95 % CI 1.18–1.75; p-trend = 0.0006). No substantial associations were observed for mortality from stroke, Alzheimer’s disease or unspecified dementia. Conclusion: These results indicate that a pro-inflammatory diet, as evidenced by higher DII scores, may be associated with total mortality as well as mortality from digestive cancer, CVD, CHD and COPD.