Objective The objective of this study was to determine if supportive care without endotracheal intubation in the emergency department (ED) was safe in the absence of complications in gamma-hydroxybutyrate (GHB)/gamma-butyrolactone (GBL) intoxicated patients with a decreased Glasgow Coma Scale (GCS) score. Methods This was a retrospective chart review of patients presenting to a Dutch tertiary urban ED with a reduced level of consciousness related to alleged GHB/GBL intoxication between April 2011–December 2014. Primary endpoint was major adverse events, defined by: upper airway obstruction not resolved with mayo tube or nasopharyngeal airway, hypoxia not resolved with 15 l of oxygen delivered via non-rebreathing mask, bradypnea not resolved after stimulation, intubation, bradycardia not resolved after intravenous atropine bolus, hypotension for which inotropes were started. Results Data of 209 patients were retrieved. Major adverse events were reported in five patients (2.4%; 95% CI: 0.8–5.5). Intubation with subsequent ICU admission was required for 1.4% of patients (95% CI: 0.3–4.1). The most frequently seen minor adverse events (N = 209) were: airway obstruction (22%), hypothermia (14.8%), hypoxia (12.9%), bradycardia (8.1%), hypotension (6.7%), bradypnea (5.7%), vomiting (5.3%). There were no deaths. None of the patients had signs of aspiration pneumonia or returned to our ED due to complications. Conclusion Our study suggests that conservative airway management for patients with a decreased GCS due to suspected GHB intoxication may be safe. Major adverse events were present in 2.4% of patients, only 1.4% of patients required intubation. All minor adverse events were managed effectively with conservative treatment.