We hypothesised that increased on-admission and follow-up mean platelet volume (MPV) levels would correlate with adverse outcomes in patients with infective endocarditis (IE). A total of 108 consecutive patients were grouped into two according to median MPV level (≤ 8.6 and > 8.6 fL). Patients with MPV level of > 8.6 fL had a significantly higher rate of end-stage renal disease, Staphylococcus aureus infection, higher CRP levels, embolic events and in-hospital mortality compared to patients with MPV levels ≤ 8.6 fL. In multivariable Cox regression analysis, previous history of IE, S. aureus infection, end-stage renal disease, depressed LVEF, early surgical intervention, vegetation size ≥ 10 mm, presence of perivalvular abscess, higher on-admission platelet count, CRP and MPV levels emerged as independent predictors of in-hospital unfavourable outcomes. Patients with embolic events and in-hospital mortality revealed an incremental trend for MPV levels compared to patients without any adverse events. Our study results suggest that both on-admission and follow-up MPV levels may be a simple and available biomarker for risk stratification of IE patients.