The Glasgow Coma Scale (GCS) characterizes patients with diminished consciousness. In a recent systematic review, we found overall adequate reliability across different clinical settings, but reliability estimates varied considerably between studies, and methodological quality of studies was overall poor. Identifying and understanding factors that can affect its reliability is important, in order to promote high standards for clinical use of the GCS.The aim of this systematic review was to identify factors that influence reliability and to provide an evidence base for promoting consistent and reliable application of the GCS.A comprehensive literature search was undertaken in MEDLINE, EMBASE, and CINAHL from 1974 to July 2016. Studies assessing the reliability of the GCS in adults or describing any factor that influences reliability were included. Two reviewers independently screened citations, selected full texts, and undertook data extraction and critical appraisal. Methodological quality of studies was evaluated with the consensus-based standards for the selection of health measurement instruments checklist. Data were synthesized narratively and presented in tables.Forty-one studies were included for analysis. Factors identified that may influence reliability are education and training, the level of consciousness, and type of stimuli used. Conflicting results were found for experience of the observer, the pathology causing the reduced consciousness, and intubation/sedation. No clear influence was found for the professional background of observers.Reliability of the GCS is influenced by multiple factors and as such is context dependent. This review points to the potential for improvement from training and education and standardization of assessment methods, for which recommendations are presented.