We studied ten healthy, nonsmoking adults to determine the intra-subject variability for repeated measurements of transcutaneous oxygen pressure (tcPO2) and oxygen saturation by pulse oximetry (SaO2). Intra-subject variability was less for SaO2 than for tcPO2 and increased at lower arterial oxygen tensions. Inter-machine variability was an important contributor to intra-subject variability for tcPO2. The percentage change from baseline required to detect a significant physiologic change while breathing room air was 1.2 percent for SaO2 and 13.8 percent for tcPO2. When subjects breathed a 15 percent oxygen mixture, the percentage change for significance increased to a maximum of 4.7 percent for SaO2 and 35.8 percent for tcPO2. These results are applicable to non-neonatal pediatric and adult patients and demonstrate the importance of intra-subject variability when performing noninvasive measurements of patient oxygenation over time.