Background and study aims: Several studies have shown that insufflation of carbon dioxide (CO2) instead of air dur-ing colonoscopy can reduce postprocedural pain. However, CO2 insufflation might also lead to CO2 retention in the human body. It was recently shown that this side effect does not occur in unsedated patients, but that sedation leads to impaired respiration. Sedated patients may therefore be more prone to CO2 retention. This randomized, double-blinded study was designed to investigate whether CO2 insufflation leads to CO2 retention in sedated patients. Patients and methods: A total of 103 consecutive patients undergoing colonoscopy were randomly assigned to the use of either CO2 or air insufflation. End-tidal carbon dioxide (ETCO2), a noninvasive parameter for arterial PCO2, was recorded before the examination, twice during it, and 10 min after it. Midazolam or pethidine, or both, were used for sedation. The patient’s pain during the examination and 1, 3, 6, and 24 h afterwards was registered using a questionnaire. Results: CO2 was used in 52 patients and air insufflation in 51. A total of 52 patients (51% ) received sedation. There were no differences in ETCO2 between the CO2 and air group. A slight increase in ETCO2 was observed in sedated patients, while there was no increase in unsedated patients. CO2 insufflation significantly reduced pain after the procedure at all time points. Conclusions: This study indicates that CO2 insufflation reduces pain and is safe to use in colonoscopy for sedated patients. However, CO2 insufflation might also lead to CO2 retention in the human body. It was recently shown that that This randomized, double-blinded study was designed to investigate whether CO2 insufflation leads to impaired respiration. Patients and methods: A total of 103 consecutive patients undergoing colonoscopy were randomly assigned to the use of either CO2 or air insufflation. End-tidal carbon dioxide (ETCO2), a noninvasive parameter for arterial PCO2, was recorded before the examination, twice during it , and 10 min after it. Midazolam or pethidine, or both, were used for sedation. The patient’s pain during the examination and 1, 3, 6, and 24 h afterwa Results: CO2 was used in 52 patients and air insufflation in 51. A total of 52 patients (51%) received sedation. There were no differences in ETCO2 between the CO2 and air group. A slight increase in ETCO2 was observed in sedated patients, while there was no increase in unsedated patients. CO2 insufflation significantly reduced pain after the procedure at all time points. Conclusions: This study indicates that CO2 insufflation reduces pain and is safe to use in colonoscopy for sedated patients.