BACKGROUND Many anesthetics reduce lower esophageal sphincter pressure (LESP) and consequently the gastro-esophageal pressure gradient (GEPG); thus they may promote gastro-esophageal reflux and contribute to aspiration pneumonia. Our goals were to evaluate the association between LESP and 2 measures of sedation: bispectral index (BIS) and the responsiveness component of the Observer's Assessment of Alertness score (OAA/S). MATERIAL/METHODS Eleven healthy volunteers were each sedated on 2 separate days. Subjects were given sedative infusions of increasing target plasma concentrations of dexmedetomidine or propofol. LESP and GEPG were recorded after starting each infusion phase. Generalized estimating equation modeling was used to assess the relationship between LESP and, respectively, BIS and OAA/S. The existence of a drug-dependent association was evaluated within these models by testing an interaction term. Wald tests were used to evaluate the relationships within the models. RESULTS We found a significant relationship between LESP and BIS (P=0.0043) after adjusting for the main effect of sedative type--a deepening of sedation as measured by a decrease in BIS of 10% was associated with a decrease [Bonferroni-adjusted 95% CI] in LESP of -1.34 [-2.39, -0.29] mmHg. After adjusting for the main effect of sedative drug, LESP significantly declined with declining OAA/S (P=0.001); a unit decrease of OAA/S was associated with a decrease [Bonferroni-adjusted 95% CI] in LESP of -2.01 [-3.20, -0.81] mmHg. CONCLUSIONS Deeper sedation, as measured by either BIS or OAA/S, significantly reduces LESP.