Indirect calorimetry (IC) is the only way to measure in real time energy expenditure (EE) and to optimize nutrition support in acutely and chronically ill patients. Unfortunately, most of the commercially available indirect calorimeters are rather complex to use, expensive and poorly accurate and precise. Therefore, an innovative device (Q-NRG®, COSMED, Rome, Italy) that matches clinicians' needs has been developed as part of the multicenter ICALIC study supported by the two academic societies ESPEN and ESICM. The aim of this study was to evaluate the accuracy and intra- and inter-unit precision of this new device in canopy dilution mode invitro and in spontaneously breathing adults. Accuracy and precision of oxygen consumption (VO2) and carbon dioxide production (VCO2) measurements were evaluated invitro and in 15 spontaneously breathing healthy adults by interchanging three Q-NRG® units in a random order. Invitro validation was performed by gas exchange simulation using high-precision gas mixture and mass flow controller. Accuracy was calculated as error of measured values against expected ones based on volume of gas infused. Respiratory coefficient (RQ) accuracy was furthermore assessed using the ethanol-burning test. To evaluate the intra- and inter-unit precisions, the coefficient of variation (CV%=SD/Mean*100) was calculated, respectively, from the mean±SD or the mean±SD of the three mean values of VO2, VCO2, RQ and EE measured by each Q-NRG® units. Invivo accuracy measurement of the Q-NRG® was assessed by simultaneous comparison with mass spectrometry (MS) gas analysis, using Bland-Altman plot, Pearson correlation and paired t-test (significance level of p=0.05). Invitro evaluation of the Q-NRG® accuracy showed measurement errors <1% for VO2, VCO2 and EE and <1.5% for RQ. Evaluation of the intra- and inter-unit precision showed CV% ≤1% for VO2 and EE and CV% ≤1.5% for VCO2 and RQ measurements, except for one Q-NRG® unit where CV% was 2.3% for VO2 and 3% for RQ. Very good inter-unit precision was confirmed invivo with CV% equal to 2.4%, 3%, 2.8% and 2.3% for VO2, VCCO2, RQ and EE, respectively. Comparison with MS showed correlation of 0.997, 0.987, 0.913 and 0.997 for VO2, VCO2, RQ and EE respectively (p≤0.05). Mean deviation of paired differences was 1.6±1.4% for VO2, -1.5±2.5% for VCO2, -3.1±2.6% for RQ and 0.9±1.4% for EE. Both invitro and invivo measurements of VO2, VCO2, RQ and EE on three Q-NRG® units showed minimal differences compared to expected values and MS and very low intra- and inter-unit variability. These results confirm the very good accuracy and precision of the Q-NRG® indirect calorimeter in canopy dilution mode in spontaneously breathing adults.