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Background & Aims: The ICALIC project was initiated for developing an accurate, reliable and user friendly indirect calorimeter (IC) and aimed at evaluating its ease of use and the feasibility of the EE measurements in intensive care unit (ICU)., Methods: This was a prospective unblinded, observational, multi-center study. Simultaneous IC measurements in mechanically ventilated ICU patients were performed using the new IC (Q-NRG®) and currently used devices. Time required to obtain EE was recorded to evaluate the ease of use of Q-NRG® versus currently used ICs and EE measurements were compared. Conventional descriptive statistics were used: data as mean ± SD., Results: Six centers out of nine completed the required number of patients for the primary analysis. Mean differences in the time needed by Q-NRG® against currently used ICs were -32.3 ± 2.5 min in Geneva (vs. Deltatrac®; p < 0.01), -32.3 ± 3.1 in Lausanne (vs. Quark RMR®; p < 0.05), -33.7 ± 1.4 in Brussels (vs. V-Max Encore®; p < 0.05), -26.4 ± 7.8 in Tel Aviv (vs. Deltatrac®; p < 0.05), -28.5 ± 3.5 in Vienna (vs. Deltatrac®; p < 0.05), and 0.3 ± 1.2 in Chiba (vs. E-COVX®; p = 0.17). EE (kcal/day) measurements by the Q-NRG® were similar to the Deltatrac® in Geneva and Vienna (mean differences±SD: -63.1 ± 157.8 (p = 0.462) and -22.9 ± 328.2 (=0.650)), but significantly different in Tel Aviv (307.4 ± 324.5, p < 0.001). Significant differences were observed in Lausanne (Quark RMR® :  -224.4 ± 514.9, p = 0.038) and in Brussels (V-max®: -449.6 ± 667.4, p < 0.001), but none was found in Chiba (E-COVX®; 55.0 ± 204.1, p = 0.165)., Conclusion: The Q-NRG® required a much shorter time than most other ICs to determine EE in mechanically ventilated ICU patients. The Q-NRG® is the only commercially available IC tested against mass spectrometry to ensure gas accuracy, while being very easy-to use., Competing Interests: Conflict of interest T Oshima received research grant from the public Foundation Nutrition 2000. M Delsoglio, YM Dupertuis and C Veraar have no conflict of interest. P Singer received nonrestrictive research grants and/or honoraries for lectures from Abbott, Baxter, B Braun, Fresenius-Kabi, Nestle, Nutricia and ART Medical., GE, Cosmed and Mindray. E De Waele received unrestricted research grants from the Belgian Government of Health, Baxter Healthcare, Nutricia, Fresenius Kabi International, B Braun and honoraries for lectures for Baxter, Nutricia, and Fresenius Kabi, none being related to the present study. CP Heidegger received restricted research grants from Fresenius Kabi and Nestlé, none being related to the present study. J Wernerman: received consulting fees and/or honoraries for lectures for Baxter, Fresenius Kabi, GE Health Care, Nestlé, and Nutricia none being related to the present study. P Wischmeyer received grant funding from National Institutes of Health, Canadian Institutes of Health Research, Abbott, Baxter, Fresenius and Takeda, unrestricted gift donations in support of nutrition research from Cosmed and Musclesound, honoraria or travel expenses for CME lectures on improving nutrition care from Abbott, Baxter, and Nutricia. He has served as a consultant to Abbott, Fresenius, Baxter, Cardinal Health, Nutricia and Takeda for ICU nutrition research. MM Berger received unrestricted research grant from Fresenius Kabi International, consulting fees from Fresenius Kabi International, and honoraries for lectures for Fresenius Kabi, Nestlé, and Baxter, none being related to the present study. C Pichard received financial support from research grants and unrestricted academic research grants from the public institutions, as well as no-restrictive research grants and consulting fees from the Foundation Nutrition 2000plus, Abbott, Baxter, B. Braun, Cosmed, Fresenius-Kabi, Nestle Medical Nutrition, Novartis, Nutricia-Numico, Pfizer, Shire and Solvay., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)