The Masimo Radical-7 Pulse CO-Oximeter (Masimo Corp., USA) non-invasively computes hemoglobin concentration (SpHb). SpHb was compared to Co-Oximeter readings (CoOxHb) of arterial samples in surgery patients of the emergency department. Forty-six patients were enrolled. The Masimo R1 25L (revision F and G) adult adhesive sensor was attached to the ring finger of the arterially cannulated hand. Before start, every 30 min during surgery and in the case of severe bleeding SpHb and CoOxHb values were documented. SpHb and post hoc adjusted SpHb (AdSpHb) values were analyzed. Linear regression analysis and Bland-Altman plot for agreement were performed. The detection failure rate of SpHb was 24.5 %. CoOxHb and SpHb showed a strong correlation (r = +0.81), but agreement was moderate [bias (LOA) of -0.6 (-3.0; +1.9)] g/dl. Positive and negative predicted value was 0.49 and 0.69. Exclusion of changes of CoOxHb values ≤1 g/dl resulted in a positive and negative predictive value of 0.66 and 1.00. Post hoc adjustment of the SpHb (AdSpHb) improved linear correlation of CoOxHb and AdSpHb [r = +0.90 (p < 0.001)] but less the agreement [bias (LOA) of CoOxHb and AdSpHb = -0.1 (-2.1/+1.9) g/dl]. SpHb agreed only moderately with CoOxHb values and predicted decreases of CoOxHb only if changes of SpHb ≤ 1.0 g/dl were excluded. The detection failure rate of SpHb was high. At present, additional refinements of the current technology are necessary to further improve performance of non-invasive hemoglobin measurement in the clinical setting.