Mean platelet volume (MPV) is an index of platelet function that reflects platelet production rate and sensitivity to activation. The relationship between MPV and coronary vasospasm has not been previously studied. In this study, we aimed to evaluate this relationship. A total of 696 patients (age 55.20 ± 12.26, male 46.4%, female 53.6%) with typical or atypical angina who underwent diagnostic coronary angiography (CAG) and an acetylcholine (Ach)-provocation test were enrolled. Each patient was assigned to either an Ach-induced coronary vasospasm group (n = 183) or a control group (n = 513). We compared MPV between the two groups. MPV and the platelet count showed a negative correlation (r = -0.289, p < 0.001). MPV was higher in the Ach-induced coronary vasospasm group than in the control group (9.03 ± 1.37 fl and 8.69 ± 1.25 fl, respectively, p = 0.002). In multivariate analysis, MPV independently predicted Ach-induced coronary vasospasm (OR = 1.188, p = 0.018). This study identified high MPV as an independent risk factor for Ach-induced coronary vasospasm.