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Propofol, a short-acting hypnotic drug, is increasingly administered by a diverse group of specialists (e.g., cardiologists, gastroenterologists) during diagnostic and therapeutic procedures. Standard monitoring during sedation comprises continuous pulse oximetry with visual assessment of the patient’s breathing pattern. Because undetected hypoventilation is a common pathway for complications, capnographic monitoring of exhaled carbon dioxide has been advocated. We examined whether the use of capnography reduces the incidence of hypoxemia during nonanesthesiologist-administered propofol sedation in patients who did not receive supplemental oxygen routinely.An open, stratified, randomized controlled trial was conducted in 427 healthy adult women during minor gynecology procedures in an outpatient clinic in the Netherlands. Patients were randomly assigned to receive either standard respiratory monitoring (standard care) or standard respiratory monitoring combined with capnography (capnography group). To replicate usual clinical practice, capnography monitoring was performed by the same medical team that provided sedation. The primary end point was the incidence of hypoxemia, defined as oxygen saturations <91%.From April 2010 to January 2011, 427 patients were enrolled. In the capnography group, 206 patients and in the standard care group, 209 patients were analyzed. The percentage of patients with a hypoxemic episode was 25.7% (53 of 206) in the capnography group and 24.9% (52 of 209) in the standard care group, resulting in an absolute difference of 0.8% (−7.5 to 9.2%).We were unable to confirm an additive role for capnography in preventing hypoxemia during elective nonanesthesiologist-administered propofol (monotherapy) sedation in healthy women in whom supplemental oxygen is not routinely administered. Based on the confidence interval, the benefit of adding capnography is at most an absolute hypoxemia reduction of 7.5%, suggesting that adding it in this practice setting to the routine monitoring strategy does not necessarily improve patient safety in daily practice.