Background: Adequate pre-operative anxiolysis and sedation are important in patients undergoing surgery. Agomelatine and Ramelteon are analogues of melatonin and have been used routinely to induce sleep in insomnia patients. Aims: To compare the effects of Tab. agomelatine and Tab. ramelteon on pre-operative anxiety, sedation and orientation. Subjects and Methods: This was a prospective, randomized, comparative study conducted after institutional ethics committee approval on 60 ASA I adult patients undergoing elective surgeries under general anesthesia. After obtaining written and informed consent, the patients were randomly allocated into two equal groups: Group A (n = 30) received Tab. agomelatine 10 mg and Group R (n = 30) received Tab. ramelteon 8 mg orally, 1 hour before induction of anesthesia. Patient’s anxiety, sedation and orientation were assessed at 0, 15, 30, 45, 60 minutes and before induction of anesthesia. Statistical Analysis: Statistical software namely SAS 9.2, SPSS 15.0, Stata 10.1, MedCalc 9.0.1, Systat 12.0 and R environment ver. 2.11 were used for analysis of data. Data was expressed as mean ± standard deviation or absolute values. Qualitative data were compared with the Chi-square test and fisher's exact test. Quantitative variables were compared with the student 't' test. The level of statistical significance was set at p < 0.05. Results: Decrease in anxiety levels from baseline in both the groups and greatest reduction was at 15 minutes. In both the groups, increasing sedation score was noted after 15 minutes and greatest sedation around 60 minutes. Orientation score between the two groups was unchanged from baseline and between the two groups as well and hence no p-value. Conclusion: Tab. agomelatine 10 mg and Tab. Ramelteon 8 mg administered orally, 60 minutes before induction of anesthesia provided comparable anxiolysis and sedation but did not affect orientation of the patient.