Abstract. Comparability and reproducibility of different near-infrared spectroscopy devices measuring regional tissue oxygen saturation remain poor. Aim of the present study was to compare values and reproducibility of cerebral/peripheral "tissue-oxygenation-index" (TOI; NIRO 300, Hamamatsu R , Japan) with cerebral/peripheral "regional-oxygen-saturation" (rSO; INVOS5100, Somanetics R , USA), and to analyze the influence of quality criteria. Methods: cTOI and crSO2 were measured on the left forehead, pTOI and prSO2 were measured on the left calf. To analyse reproducibility, optodes were reapplied five times. A quality criterion was introduced for cTOI, crSO2 and prSO2. For pTOI quality criteria were introduced in combination with a venous occlusion technique. Results: Cerebral measurements were performed in 37 neonates. cTOI (72.7 + / − 6.2%) was lower than crSO2 (83.3 + / − 5.8%) (p < 0.001). The mean difference between cTOI and crSO2 was 10%. Mean standard deviations of cTOI and crSO2 were similar (cTOI: 4.9 + / − 3.6; crSO2: 4.5 + / − 2.6). Peripheral measurements were performed in 39 neonates. pTOI (66.0 + / − 7.9%) was lower than prSO2 (82.0 + / − 7.0%)(p < 0.001). The mean difference between pTOI and prSO2 was 15%. Mean standard deviations of pTOI (3.7 + / − 2.6%) were lower than of prSO2 (5.0 + / − 3.0%) (p = 0.047). Conclusion: TOI values were significantly lower than rSO2 values, in cerebral and peripheral measurements. Reproducibility was higher for pTOI than for prSO2. C 2011 Society of Photo-Optical Instrumentation Engineers (SPIE).