For the first time, thrust force, power consumption, flank tool wear using FE-SEM and line scan EDS analysis; hole quality indicators and hole surface analysis using FE-SEM, microhardness and chip morphology for drilling Ti-6Al-4V using cryogenic coolants (LN2 and LCO2) and flood coolant are comprehensively investigated. 146 blind holes are drilled for all three cooling conditions. 72% and 50% lesser tool wear is observed for LCO2 and LN2 respectively, compared to flood machining. Adhesion wear mechanism is found to be the predominant factor leading to higher tool wear during flood machining. The demonstrated superior performance of LCO2 for all the machinability indicators in this research is a significant finding for machining Ti-6Al-4V for the high-value manufacturing industries. •Extensive comparison is made in drilling Ti-6Al-4V with flood and cryogenic LN2 and LCO2.•Thrust force, microhardness and chip morphology are studied for the various cutting fluid strategies.•Industry relevant gauges like tool wear and hole surface indicators are studied.•LCO2 is found to be sustainable providing better machining performance than others.