Aim: To assess and compare efficacy and safety of Eszopiclone in patients suffering from insomnia. Design: Randomized, multicentric, comparative clinical trial. Materials and Methods: Adult patients suffering from short-term/transient/chronic insomnia were enrolled after obtaining written informed consent and subjected to a washout (no drug) period for first 4 days followed by 7 days treatment with Eszopiclone 3 mg OD. After eszopiclone treatment, patients were randomly allocated to any one of the four drugs viz. zopiclone 7.5 mg OD, zolpidem 10 mg OD, zaleplon 10 mg OD and nitrazepam 5 mg OD for next 7 days. Patients were given patient diary cards for recording sleep parameters and were followed-up thrice, on day 5, day 12 and day 19 when assessment of improvement in sleep parameters and side-effect profile was done. Results: A total of 100 patients completed the study. Baseline total sleep time (minutes, mean ± SD) in the Eszopiclone 3 mg (n=100), Zopiclone 7.5 mg (n=27), Zaleplon 10 mg (n=24), Zolpidem 10 mg (n=23) and Nitrazepam 5 mg (n=26) treated groups increased significantly (P<0.001) from 327.5 ± 105.3 to 438.34 ± 105.3; 345.7 ± 98.03 to 454.71 ± 122.3; 291 ± 89.73 to 430.39 ± 76.73; 311 ± 125.8 to 441.12 ± 107.65 and 356.8 ± 99.21 to 456.68 ± 67.41 respectively. Baseline sleep latency time (minutes, mean ± SD) and number of awakenings (mean ± SD) in the Eszopiclone, Zopiclone, Zaleplon, Zolpidem and Nitrazepam treated groups decreased (P<0.001) from 117.15 ± 72.38 and 1.91 ± 1.1 to 36.89 ± 20 and 0.78 ± 0.65; 127.73 ± 59.03 and 1.61 ± 0.92 to 45.14 ± 24.86 and 0.77 ± 0.75; 108.13 ± 78.7 and 1.9 ± 1.04 to 40.95 ± 18.01 and 0.9 ± 0.56; 131.52 ± 95.18 and 2.25 ± 1.58 to 38.93 ± 26.43 and 0.89 ± 0.57; 101.78 ± 53.09 and 1.93 ± 0.7 to 34.12 ± 11.8 and 0.69 ± 0.64 respectively. There was no statistically significant (P>0.05) difference between-groups in improving total sleep time and sleep latency. The overall incidence of side-effects was: Eszopiclone (39%), Zopiclone (51.85%), Zolpidem (52.17%), Zaleplon (33.33%) and Nitrazepam (50%). Conclusion: Eszopiclone was effective and comparable to other treatments in improving the sleep parameters in patients suffering from insomnia with better safety profile than Zopiclone, Zolpidem and Nitrazepam.