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Abstract Background Usual clinical practice for arterial blood gas analysis (BGA) in conscious patients involves a one-time arterial puncture to be performed after a resting period of 20–30 min. The aim of this study was to evaluate the use of transcutaneous BGA for estimating this gold standard arterial BGA. Methods Spontaneously breathing Asian adults (healthy volunteers and respiratory patients) were enrolled (n = 295). Transcutaneous PO2 (PtcO2) and PCO2 (PtcCO2) were monitored using a transcutaneous monitor (TCM4, Radiometer Medical AsP, Denmark) with sensors placed on the chest, forearm, earlobe or forehead. Transcutaneous BGA at 1-min intervals was compared with arterial BGA at 30 min. Reasonable steps to find severe hypercapnia with PaCO2 > 50 mmHg were evaluated. Results Sensors on the chest and forearm were equally preferred and used because of small biases (n = 272). The average PCO2 bias was close to 0 mmHg at 4 min, and was almost constant (4–5 mmHg) with PtcCO2 being higher than PaCO2 at ≥8 min. The limit of agreement for PCO2 narrowed over time: ± 13.6 mmHg at 4 min, ± 7.5 mmHg at 12–13 min, and ± 6.3 mmHg at 30 min. The limit of agreement for PO2 also narrowed over time (± 23.1 mmHg at 30 min). Subgroup analyses showed that the PaCO2 and PaO2 levels, gender, and younger age significantly affected the biases. All hypercapnia subjects with PaCO2 > 50 mmHg (n = 13) showed PtcCO2 ≥ 50 mmHg for until 12 min. Conclusions Although PtcCO2 is useful, it cannot completely replace PaCO2 because PCO2 occasionally showed large bias. On the other hand, the prediction of PaO2 using PtcO2 was unrealistic in Asian adults. PtcCO2 ≥ 50 mmHg for until 12 min can be used as a screening tool for severe hypercapnia with PaCO2 > 50 mmHg.