The inter-relationships between infarct size and diastolic dysfunction following MI have not been well studied. This study sought to define the determinants of severe DD (restrictive mitral inflow pattern on Doppler echocardiography [RFP]) in patients with first-ever MI, with particular emphasis on the impact of infarct size. Retrospective single-centre study including consecutive patients with a first-ever non-ST-elevation-MI (NSTEMI) or ST-elevation-MI (STEMI) (n=477). Peak Troponin-I (Peak-TnI) was used as principal measure of infarct size, whilst LVEF and wall motion score index (WMSI) were regarded as surrogate measures. Echocardiography was performed within 24 hours of admission for all patients. RFP was defined as E/A ratio >2.0 or E/A ratio >1.5 and E-wave deceleration time <140ms. A total of sixty-nine patients (14.5%) had RFP. Peak-TnI levels were higher in the RFP group (32.6±32.7 versus 16.9±25.2μg/L, p<0.001). In sequential multivariable models incorporating significant clinical, angiographic and LV size-related variables, Peak-TnI (OR 1.98, p=0.001), WMSI (OR 2.34, p=0.048) and LVEF (OR 0.97,p=0.044) were weak independent correlates of RFP. Presence of diabetes was also an independent predictor in all the models constructed. When patients were stratified according to an LVEF of 50%, 39% of RFP patients had a preserved LVEF (RFP/preserved EF group), and these patients had lower Peak-TnI levels compared to the RFP/reduced EF group (14.4±18.7 vs 44.5±35.5 μg/L, p=0.001). The relationship between infarct size and LV diastolic dysfunction is bimodal: patients with high Troponin/ low LVEF have predominantly infarct related diastolic dysfunction; whereas patients with low TnI/ preserved LVEF have predominantly pre-existing diastolic dysfunction.