Prophylactic prasugrel for endovascular treatment of intracranial aneurysms has been introduced and increased, but HTPR (high on-treatment platelet reactivity) or LTPR (low on-treatment platelet reactivity) of prasugrel is not uncommon in clinical circumstances. To investigate the predisposing factors of HTPR and LTPR on prasugrel premedication in the neurointerventional field and to determine its clinical implications. Between February 2016 and December 2020, 191 patients treated with coil embolization using prophylactic prasugrel in 234 intracranial aneurysms were the final candidates for this study. Patient and aneurysm characteristics, clinical status, and laboratory study values were carefully reviewed retrospectively. We performed risk factor analyses for HTPR and LTPR on prasugrel. Ultimately, 20 patients (10.5%) had HTPR, and 74 patients (38.7%) were categorized as having LTPR. In multivariable analyses, the factors related to HTPR were BMI (adjusted OR 1.21, 95% CI 1.04-1.41, p = 0.01), history of antithrombotics (adjusted OR 3.79, 95% CI 1.39-10.34, p = 0.01), and hematocrit (adjusted OR 0.91, 95% CI 0.84-0.99, p = 0.03). Low BMI was the only risk factor for LTPR (adjusted OR 0.84, 95% CI 0.76-0.94, p = 0.001). In the neurointerventional field, high BMI and prior use of antithrombotic agents were related to HTPR, and low BMI was associated with LTPR on prophylactic prasugrel. High hematocrit levels decreased the risk of HTPR. When preparing endovascular treatment for intracranial aneurysms, attention to patients with these clinical features is required to address the possibility of ischemic or bleeding complications.