For many years, pulse oximetry has been widely used in the clinical environment for a reliable monitoring of oxygen saturation (SpO 2) and heart rate. But since common sensors are mainly placed to peripheral body parts as finger or earlobe, it is still highly susceptible to reduced peripheral perfusion, e.g., due to centralization. Therefore, a novel in-ear pulse oximetric sensor (placed against the tragus) was presented in a prior work which is deemed to be independent from perfusion fluctuations due to its proximity to the trunk. Having demonstrated the feasibility of in-ear S pO2 measurement with reliable specificity in a laboratory setting, we now report results from a study on in-ear SpO2 in a clinical setting. For this, trials were performed on 29 adult patients undergoing surgery. In-ear SpO2 data are compared with SaO2 data obtained by blood gas analysis, and with three reference pulse oximeters applied to the finger, ear lobe, and forehead. In addition, we derived an SpO2-independent perfusion index by means of the wavelengths used. The feasibility and robustness of in-ear SpO2 measurement is demonstrated under challenging clinical conditions. SpO2 shows good accordance with SaO2, a high level of comparability with the reference pulse oximeters, and was significantly improved by introducing a new algorithm for artifact reduction. The perfusion index also shows a good correlation with the reference data.