Chronic diseases such as cancer and cardiovascular diseases (CVDs) are well-established causes of disability and premature death. Dietary components have been implicated in the etiology of these chronic diseases. We examined the ability of the Dietary Inflammatory Index (DIITM) to predict all-cause, coronary heart disease (CHD), CVD and cancer mortality and incident CHD in the MONICA-KORA Cohort Studies. DII scores were computed from baseline 7-day dietary records in this cohort of 1297 men, who were aged 45-64 years when enrolled. During the follow-up period, 551 total (155 CHD, 244 CVD and 175 cancer-related deaths) and 213 validated incident CHD events were identified through mortality record linkage and active follow-up. Spearman correlation coefficients were calculated between DII scores and the inflammatory marker C-reactive protein (CRP). Cox proportional hazards regression was used to estimate hazard ratios (HR) for the endpoints described above. DII scores were significantly positively correlated with CRP (P value < 0.0001). Positive associations were noted between DII and all-cause mortality (HRQ4vsQ1: 1.41; 95%CI 1.04-1.90;P-trend = 0.007) and incident CHD (HRQ4vsQ1: 1.83; 95%CI 1.12-3.01; P-trend = 0.008). These associations were attenuated after further adjustment for smoking status, but remained significant for all-cause mortality. When stratified by smoking status, DII was associated with all-cause and cancer mortality among ex-smokers, in the absence of significant heterogeneity. These results indicate that a pro-inflammatory diet as expressed by higher DII scores is associated with all-cause mortality. This association was more pronounced among ex-smokers in whom a significant association with cancer mortality was observed.