Arterial carbon dioxide partial pressure measurements using the NBP-75® microstream capnometer were compared with direct PaCO2 values in patients who were (a) not intubated and spontaneously breathing, and (b) patients receiving intermittent positive pressure ventilation of the lungs and endotracheal anaesthesia. Twenty ASA physical status I–III patients, undergoing general anaesthesia for orthopaedic or vascular surgery were included in a prospective crossover study. After a 20-min equilibration period following the induction of general anaesthesia, arterial blood was drawn from an indwelling radial catheter, while the end-tidal carbon dioxide partial pressure was measured at the angle between the tracheal tube and the ventilation circuit using a microstream capnometer (NBP-75®, Nellcor Puritan Bennett, Plesanton, CA, USA) with an aspiration flow rate of 30 mL min−1. Patients were extubated at the end of surgery and transferred to the postanaesthesia care unit, where end-tidal carbon dioxide was sampled through a nasal cannula (Nasal FilterLine, Nellcor, Plesanton, CA, USA) and measured using the same microstream capnometer. In each patient six measurements were performed, three during mechanical ventilation and three during spontaneous breathing. A good correlation between arterial and end-tidal carbon dioxide partial pressure was observed both during mechanical ventilation (r = 0.59; P = 0.0005) and spontaneous breathing (r = 0.41; P = 0.001); while no differences in the arterial to end-tidal carbon dioxide tension difference were observed when patients were intubated and mechanically ventilated (7.3 ± 4 mmHg; CI95: 6.3–8.4) compared to values measured during spontaneous breathing in the postanesthesia care unit, after patients had been awakened and extubated (6.5 ± 4.8 mmHg; CI95: 5.2–7.8) (P = 0.311). The mean difference between the arterial to end-tidal carbon dioxide tension gradient measured in intubated and non-intubated spontaneously breathing patients was 1 ± 6 mmHg (CI95: -11–+13). We conclude that measuring the end-tidal carbon dioxide partial pressure through a nasal cannula using the NBP-75® microstream capnometer provides an estimation of arterial carbon dioxide partial pressure similar to that provided when the same patients are intubated and mechanically ventilated.