The aim of the study was to analyse mortality after a first myocardial infarction (MI) and its trends in people with diabetes compared to those without diabetes in Southern Germany, 1985-2009. Using data of the population-based MONICA/KORA Myocardial Infarction Registry, we ascertained all patients with a first fatal or non-fatal MI between 1985 and 2009 (n = 16,478, age 25-74 years, 71% male, 29% with diabetes). The impact of diabetes and calendar time on mortality was examined using multiple logistic and Cox regression. Survival improved with calendar time: The crude cumulative 5-year survival was 26.9 and 46.3% among diabetic and non-diabetic individuals (both sexes combined) with a first MI in the years 1985-1989, and 53.6 and 66.6% among those with a first MI in the years 2005-2009. This significant decrease of mortality was confirmed in multivariate analyses. The proportion of fatal first MIs was significantly higher in diabetic compared to non-diabetic patients [adjusted odds ratio (OR) 1.26; 95% confidence interval 1.17-1.36]. This association persisted in a similar manner between both sexes with no consistent change of OR over calendar time in which first MIs have been observed. Likewise, multiple adjusted risk of death after a non-fatal first MI was significantly higher among both diabetic men and women [hazard ratio (HR) 1.64; 1.47-1.82, 1.83; 1.55-2.14] with constant HR over calendar time. During the past 25 years, survival has improved in both diabetic and non-diabetic patients with incident MI in a similar manner. However, mortality after a first MI remained significantly higher in the diabetic population, particularly in women.