Background: Safety and economy are the main concerns while using low- flow anaesthesia with newer inhalational agents. Aim: to compare characteristics of Desflurane with Isoflurane under low flow anaesthesia using equilibration time. Material and methods: This prospective study was done the Department of Anaesthesia ICARE Institute of Medical Science and Research, Haldia, West Bengal, India, for six months. 100 healthy patients of either sex scheduled for routine surgeries, American Society of Anaesthesiologists’ (ASA) physical status I and II, age 20–60 years, and hemoglobin more than 10 g/dL were include in this study. Patients were randomly allocated to two groups. Group I received desflurane as the inhalational anesthetic agent with minimal flow anesthesia (n=50). Group II received isoflurane as anesthetic agent with minimal flow anesthesia (n=50). Results: 100 adult patients were studied. The groups were randomly divided into two groups of 50 patients each. Mean of time taken for equilibration of the volatile anesthetic agent in the desflurane group was 5.23 ± 1.63 min and in the isoflurane group was 17.011±9.64 min, and the difference was statistically significant (P <0.001). At 5, 20, 60, and 120 min, mean endtidal concentrations (in kPa) of desflurane were not changed much and were 4.68 ± 0.80, 4.78 ± 0.62, 4.38 ± 0.61 and 4.15 ± 0.62, respectively. In the isoflurane group, variation were significant over time and were 0.77 ± 0.17, 0.93 ± 0.17, 0.73 ± 0.19 and 0.74 ± 0.19 at 5, 20, and 120 min intervals, respectively. Uptake of nitrous oxide was 80% and above by the time equilibration of any of the agents occurred. In both the groups, end-tidal to inspired nitrous oxide ratio was found to be 0.77 ± 0.14 in 5 min duration and 0.96 ± 0.03 by 12 min. Nitrous oxide concentration also fell over the time, and it was difficult to maintain nitrous oxide at 66 vol.% . It ranged between 42.30 ±4.57 and 61.20 ± 4.56. In long duration, minimal flow anesthesia nitrous oxide end-tidal concentration found to be <50%. At 80% uptake point of nitrous oxide, uptake of only desflurane was found to be nearly 80% at that time. Conclusion: we concluded that, with availability of agents like desflurane we can use minimal flow anesthesia more efficiently, with less drift in anesthetic gases and a clear-headed recovery and minimum operating room pollution