This article provides guidelines for neuroprognostication in critically ill adults with moderate-to-severe traumatic brain injury (msTBI). The authors conducted a systematic narrative review using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to assess the reliability of major clinical predictors and prediction models. After screening 8125 articles, 41 studies met the eligibility criteria. Ten clinical variables and nine grading scales were selected. The presence of bilateral pupillary nonreactivity on admission, when assessed accurately without confounding factors, was deemed moderately reliable for counseling surrogates regarding 6-month functional outcomes or in-hospital mortality. Prediction models such as CRASH-basic, CRASH-CT, IMPACT-core, IMPACT-extended, and IMPACT-lab were recommended as moderately reliable for predicting 14-day to 6-month mortality and functional outcomes. The guidelines emphasize the importance of acknowledging substantial uncertainty in prognosis when using these predictors and models. The article also includes good practice recommendations for neuroprognostication, emphasizing the need for comprehensive clinical assessment and careful consideration of all available evidence.This article provides guidelines for neuroprognostication in critically ill adults with moderate-to-severe traumatic brain injury (msTBI). The authors conducted a systematic narrative review using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to assess the reliability of major clinical predictors and prediction models. After screening 8125 articles, 41 studies met the eligibility criteria. Ten clinical variables and nine grading scales were selected. The presence of bilateral pupillary nonreactivity on admission, when assessed accurately without confounding factors, was deemed moderately reliable for counseling surrogates regarding 6-month functional outcomes or in-hospital mortality. Prediction models such as CRASH-basic, CRASH-CT, IMPACT-core, IMPACT-extended, and IMPACT-lab were recommended as moderately reliable for predicting 14-day to 6-month mortality and functional outcomes. The guidelines emphasize the importance of acknowledging substantial uncertainty in prognosis when using these predictors and models. The article also includes good practice recommendations for neuroprognostication, emphasizing the need for comprehensive clinical assessment and careful consideration of all available evidence.