BackgroundPrevious studies have shown that cortical superficial siderosis (cSS) can increase hematoma volume and predict poor outcomes following primary intracerebral hemorrhage (ICH).ObjectiveWe aimed to determine whether a large hematoma volume was the essential factor contributing to worse outcomes of cSS.MethodsPatients with spontaneous ICH underwent a CT scan within 48 h after ictus. Evaluation of cSS was performed using magnetic resonance imaging (MRI) within 7 days. The 90-day outcome was assessed using the modified Rankin Scale (mRS). In addition, we investigated the correlation between cSS, hematoma volume, and 90-day outcomes using multivariate regression and mediation analyses.ResultsAmong the 673 patients with ICH [mean (SD) age, 61 (13) years; 237 female subjects (35.2%); median (IQR) hematoma volume, 9.0 (3.0–17.6) ml], 131 (19.5%) had cSS. There was an association between cSS and larger hematoma volume (β = 4.449, 95% CI 1.890–7.009,p< 0.001) independent of hematoma location and was also related to worse 90-day mRS (β = 0.333, 95% CI 0.008–0.659,p= 0.045) in multivariable regression. In addition, mediation analyses revealed that hematoma volume was an essential factor mediating the effect of cSS on unfavorable 90-day outcomes (proportion mediated:66.04%,p= 0.01).ConclusionLarge hematoma volume was the major charge of directing cSS to worse outcomes in patients with mild to moderate ICH, and cSS was related to a larger hematoma in both lobar and non-lobar areas.Clinical trial registrationhttps://clinicaltrials.gov/ct2/show/NCT04803292, identifier: NCT04803292.