Background: Mean platelet volume (MPV) has been shown to be an independent risk factor for myocardial infarction in the general population. Methods: In the present cross-sectional study it was examined whether MPV may be associated with coronary heart disease (CHD) in patients in chronic hemodialysis treatment (n = 518). CHD was diagnosed if there was a history of myocardial infarction, coronary artery bypass grafting, or critical stenosis on coronary angiography. Results: Mean platelet volume in hemodialysis patients was 8.22 ± 0.06 fl. As compared with hemodialysis patients with a MPV <7.168 fl (the lower quintile limit), significantly more hemodialysis patients with a MPV >9.172 fl (the upper quintile limit) had CHD (odds ratio, 1.29; 95% confidence interval, 1.02–1.64). In a stepwise multiple logistic regression analysis MPV appeared to be an independent factor of CHD together with age, smoking, predialysis systolic blood pressure and serum triglyceride concentration. In a stepwise multiple linear regression model, MPV significantly depended on platelet count, volume of ultrafiltrate removed in one hemodialysis session, white blood cell count, treatment with beta blockers, heart rate, serum sodium and serum potassium concentrations. Additional measurements in 30 patients showed that MPV after a single hemodialysis session was not significantly different compared to predialysis values. Conclusion: From the present study it is concluded that MPV may be associated with CHD in hemodialysis patients.