Intracranial hypertension (IH) following acute phase traumatic brain injury (TBI) is associated with high mortality. Objective: This study proposes a novel parameter that may identify a potentially life-threatening IH (LTH) event and designs a machine learning model to predict LTH. Continuous recordings of intracranial pressure (ICP) and arterial blood pressure (ABP) from 273 TBI patients were used as the development dataset. The pressure-time dose (PTD) and pressure reactivity index (PRx) were calculated for each IH event, and an IH event with PRx > 0 and PTD > 5 was considered an LTH event. The association between the LTH parameters accumulated over five days and mortality was analyzed. A categorical boosting (CatBoost) model was employed to predict the occurrence of a future LTH event from the onset of IH using the ABP- and ICP-related parameters. Training and validation were performed on a total of 5,938 IH events. External performance evaluation was performed in 307 IH events included in the Cerebral Haemodynamic Autoregulatory Information System (CHARIS) database. The performance of the proposed model was evaluated through the area under the receiver operating characteristic curve (AUROC). The LTH parameters were able to distinguish between the deceased and surviving patients (AUROC > 0.7, p < 0.001). The CatBoost model predicted LTH with an AUROC = 0.7 on the external test dataset. This study demonstrated that the proposed LTH prediction model has a reasonable predictive capacity for mortality. The CatBoost model anticipates whether an IH event will develop into an LTH event. The findings of this study support the usefulness of ICP monitoring.