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Background: Current 2010 terrestrial (1Gz) CPR guidelines have been advocated by space agencies for hypogravity and microgravity environments, but may not be feasible. The aims of this study were to (1) evaluate rescuer performance over 1.5 min of external chest compressions (ECCs) during simulated Martian hypogravity (0.38Gz) and microgravity (μG) in relation to 1Gz and rest baseline and (2) compare the physiological costs of conducting ECCs in accordance with the 2010 and 2005 CPR guidelines., Methods: Thirty healthy male volunteers, ranging from 17 to 30 years, performed four sets of 30 ECCs for 1.5 min using the 2010 and 2005 ECC guidelines during 1Gz, 0.38Gz and μG simulations (Evetts-Russomano (ER) method), achieved by the use of a body suspension device. ECC depth and rate, range of elbow flexion, post-ECC heart rate (HR), minute ventilation (VE), peak oxygen consumption (VO2peak) and rate of perceived exertion (RPE) were measured., Results: All volunteers completed the study. Mean ECC rate was achieved for all gravitational conditions, but true depth during simulated microgravity was not sufficient for the 2005 (28.5 ± 7.0 mm) and 2010 (32.9 ± 8.7 mm) guidelines, even with a mean range of elbow flexion of 15°. HR, VE and VO2peak increased to an average of 136 ± 22 bpm, 37.5 ± 10.3 L·min-1, 20.5 ± 7.6 mL·kg-1·min-1 for 0.38Gz and 161 ± 19 bpm, 58.1 ± 15.0 L·min-1, 24.1 ± 5.6 mL·kg-1·min-1 for μG from a baseline of 84 ± 15 bpm, 11.4 ± 5.9 L·min-1, 3.2 ± 1.1 mL·kg-1·min-1, respectively. RPE was the only variable to increase with the 2010 guidelines., Conclusion: No additional physiological cost using the 2010 basic life support (BLS) guidelines was needed for healthy males performing ECCs for 1.5 min, independent of gravitational environment. This cost, however, increased for each condition tested when the two guidelines were compared. Effective ECCs were not achievable for both guidelines in simulated μG using the ER BLS method. This suggests that future implementation of an ER BLS in a simulated μG instruction programme as well as upper arm strength training is required to perform effective BLS in space.