Study objective: We determine whether the use of capnography is associated with a decreased incidence of hypoxic events than standard monitoring alone during emergency department (ED) sedation with propofol. Methods: Adults underwent ED propofol sedation with standard monitoring (pulse oximetry, cardiac and blood pressure) and capnography and were randomized into a group in which treating physicians had access to the capnography and a blinded group in which they did not. All patients received supplemental oxygen (3 L/minute) and opioids greater than 30 minutes before. Propofol was dosed at 1.0 mg/kg, followed by 0.5 mg/kg as needed. Capnographic and SpO2 data were recorded electronically every 5 seconds. Hypoxia was defined as SpO2 less than 93%; respiratory depression, as end tidal CO2 (etco2) greater than 50 mm Hg, etco2 change from baseline of 10%, or loss of the waveform. Results: One hundred thirty-two subjects were evaluated and included in the final analysis. We observed hypoxia in 17 of 68 (25%) subjects with capnography and 27 of 64 (42%) with blinded capnography (P=.035; difference 17%; 95% confidence interval 1.3% to 33%). Capnography identified all cases of hypoxia before onset (sensitivity 100%; specificity 64%), with the median time from capnographic evidence of respiratory depression to hypoxia 60 seconds (range 5 to 240 seconds). Conclusion: In adults receiving ED propofol sedation, the addition of capnography to standard monitoring reduced hypoxia and provided advance warning for all hypoxic events.