Abstract Introduction Platelet activation and hyperreactivity plays a pivotal role in developing intravascular thrombus in ST elevation myocardial infarction (STEMI). Mean platelet volume (MPV), which is readily available in clinical settings, has been linked to poor prognosis following STEMI. Recently, platelet-to-lymphocyte ratio (PLR) has emerged as a new marker of worse outcomes linking inflammation and thrombosis. We investigated the prognostic significance of the new marker, MPVLR, in diabetic patients with STEMI undergoing percutaneous coronary intervention (PCI). Methods A total of 623 patients with diabetes mellitus and STEMI undergoing primary PCI were enrolled and divided based on the median MPVLR on admission into two groups: group 1 (N = 266) with an MPVLR ≤ 4.46 and group 2 (N = 257) with an MPVLR > 4,46. Results Despite similar clinical features patients with elevated MPVLR (group 2) had worse angiographic characteristic suggestive of a higher thrombus burden. In-hospital and one-year mortality was higher in group 2. ROC analysis revealed moderate diagnostic value in predicting in-hospital mortality (adjusted HR 1.13; 95% CI 1.04–1.23; P = 0.003; MPVLR cut-off > 6.13) similar to that of PLR a good diagnostic value in predicting long-term mortality (adjusted HR 1.52; 95% CI 1.42–1.63; P < 0.0001; MPVLR cut-off > 5.88) better than that of PLR. MPVLR remained an independent risk factor of early and late mortality. Conclusions To the best of our knowledge, this is the first ever study that has investigated MPVLR. Despite similar clinical characteristics, patients with elevated MPVLR had worse angiographic features which may indicate a greater thrombus burden. Elevated MPVLR is an independent risk factor of early and late mortality following STEMI. In addition, it has similar value to PLR in predicting in-hospital mortality, and a better value than PLR in predicting long-term mortality.