Among acute mastoiditis (AM) complications, cerebral venous sinus thrombosis (CVST) is particularly severe, leading to increased intracranial pressure and potential neurological sequelae. Predicting the development of such complications is challenging. The aims of the present study were to evaluate the incidence, clinical characteristics, and risk factors for the development of CVST in AM. A retrospective study was conducted on children hospitalized with AM at the Meyer Children's Hospital between 2016 and 2024. Patients were divided into two groups: those with CVST (group A) and those without (group B), comparing demographic, clinical, and laboratory data. CVST was diagnosed using computed tomography (CT) and cerebral magnetic resonance angiography (MRA). To identify predictors of CVST complications, univariate and bivariate binary regression models were used. Out of 100 patients with AM, 15 (15%) developed CVST. Patients with CVST more frequently presented with fever, neurological symptoms (headache, vomiting), elevated CRP, and white blood cell counts compared to those who did not (p <
0.001, p <
0.001, p <
0.001, and p = 0.001, respectively). Streptococcus pyogenes and Streptococcus pneumoniae were more commonly encountered in patients with thrombotic complications (p = 0.024 and p = 0.05). Multivariate regression identified white blood cell (WBC) count and elevated C-reactive protein (CRP) as independent predictors of CVST in AM patients (OR: 1.14, 95% CI: 1.03-1.26, and OR: 1.10, 95% CI 1.00-1.21, p = 0.010 and p = 0.049, respectively). Conclusions: CVST is a frequent and serious complication of AM. Neurological symptoms and systemic inflammation (WBC count and CRP) are predictive indicators of CVST. Further studies are needed to develop risk algorithms for early diagnosis and to reduce sequelae. What is known: • Cerebral venous sinus thrombosis (CVST) are severe complications of acute mastoiditis, potentially leading to neurologic sequelae What is new: • An elevated inflammatory burden, namely a high C-reactive protein level and white blood cell count predict thrombotic complications in children with acute mastoiditis.