Background Deep hypothermic circulatory arrest (DHCA) is nowadays commonly used in pulmonary thromboendarterectomy (PTE). Neurological injury related to DHCA severely impairs the prognosis of patients. However, the risk factors and predictors of neurological injury are still unclear. Methods We conducted a prospective observational study, including 82 patients diagnosed as chronic thromboembolic pulmonary hypertension and underwent PTE alone in our center from December 2016 to May 2021. Demographic characteristics, clinical and surgical data, and neurological adverse events were recorded prospectively. Univariate and multivariate analyses were conducted to identify the predictors of neurological injury. Results Eleven (13.4%) patients exhibited neurological injuries after surgery. Univariate analysis showed that the duration of regional cerebral oxygen saturation (rSO(2)) under 40% (p < .001), the minimum rSO(2) (p = .006), and the percentage of decrease in rSO(2) (p = .011) were significantly associated with neurological injury. Multivariate analysis showed that the duration of rSO(2) under 40% was an independent predictor for postoperative neurological injury (odds ratio = 3.896, 95% confidence interval: 1.812-8.377, p < .001). The receiver operating characteristic curve showed that when the cut-off value was 1.25 min, its sensitivity for predicting neurological injury was 63.6% with a specificity of 88.7%. Conclusions The duration of rSO(2) under 40% is an independent predictor for neurological injury following PTE. For complicated lesions, more times of circulatory arrest were much safer and more reliable than a prolonged time of a single circulatory arrest. The circulation should be restored as soon as possible, when the rSO(2) under 40% is detected, rather than waiting for 5 min.