BACKGROUND: The apnea test is an essential component in the clinical determination of brain death, however it may incur a significant risk of complications such as hypotension, hypoxia and even cardiac arrest. We analyzed the risk factors associated with a failed apnea test during brain death assessment in order to predict and avoid these adverse events. METHODS: Medical records on apnea tests performed for brain-dead donors at our institution between January 2009 and January 2016 were retrospectively reviewed. Age, gender, etiology of brain death, use of catecholamines and results of arterial blood gas analysis (ABGA), systolic/diastolic blood pressure (SBP/DBP), mean arterial pressure and central venous pressure prior to apnea test initiation were collected as variables. A-a gradient and P(aO2)/F(iO2) were calculated for more precise assessment of the respiratory system. In total, 267 cases were divided into two groups based on those who completed the apnea test and those who failed the test. RESULTS: 13 cases failed the apnea test. Among them, seven cases failed due to severe hypotension (SBP < 60 mmHg) and the others failed due to refractory hypoxia. In terms of hemodynamic state, SBP was significantly higher in the completed test group than the failed group (126.5 ± 23.9 vs. 103 ± 15.2, respectively; p = 0.001). In ABGA, the completed test group showed significantly higher P(aO2)/F(iO2) (313.6 ± 229.8 vs. 141.5 ± 131.0, respectively; p = 0.008) and a lower A-a gradient (278.2 ± 209.5 vs. 506.2 ± 173.1, respectively; p = 0.000). In multivariable analysis, low SBP (p = 0.003) and high A-a gradient (p = 0.044) were independent risk factors associated with a failed apnea test. CONCLUSIONS: Although the unexpected adverse events during the apnea test for brain death determination do not occur frequently, they can be fatal. If a brain-dead patient has low SBP and a high A-a gradient, clinicians should pay more attention and prepare for potential complications prior to the apnea test.