Aims We assessed the relationship between diabetes and cardiac structure and function following myocardial infarction (MI) and whether diabetes influences the effect of direct renin inhibition on change in left ventricular (LV) size. Methods and Results The ASPIRE trial enrolled 820 patients 28 weeks after MI with ejection fraction ≤45 and randomized them to the direct renin inhibitor aliskiren (n= 423) or placebo (n= 397) added to standard medical therapy. Echocardiography was performed at baseline and after 36 weeks in 672 patients with evaluable paired studies. Compared with non-diabetic patients, diabetic patients (n= 214) were at higher risk for a composite of cardiovascular (CV) death, heart failure hospitalization, recurrent MI, stroke, or aborted sudden death (14 vs. 7; adjusted hazard ratio 1.63, 95 confidence interval 1.012.64, P= 0.045), despite similar left ventricular ejection fraction (37.9 ± 5.3 vs. 37.6 ± 5.2, P= 0.48) and end-systolic volume (ESV) (84 ± 25 vs. 82 ± 28 mL, P= 0.46). Diabetic patients demonstrated greater concentric remodelling (relative wall thickness 0.38 ± 0.07 vs. 0.36 ± 0.07, P= 0.0002) and evidence of higher LV filling pressure (E/E′ 11.1 ± 5.3 vs. 9.1 ± 4.3, P= 0.0011). At 36 weeks, diabetic patients experienced similar per cent reduction in ESV overall (-4.9 ± 17.9 vs.-5.5 ± 16.9, P= 0.67) but tended to experience greater reduction in ESV than non-diabetic patients when treated with aliskiren (interaction P= 0.08). Conclusions Compared with non-diabetic patients, diabetic patients are at increased risk of CV events post-MI despite no greater LV enlargement or reduction in systolic function. Diabetic patients demonstrate greater concentric remodelling and evidence of higher LV filling pressure, suggesting diastolic dysfunction as a potential mechanism for the higher risk observed among these patients. © 2011 The Author.