Several methods have been suggested to decrease bleeding during surgery, one of which is the usage of hypotensive anesthetic agents. Endoscopic Sinus Surgery (ESS) is one of the surgeries which need a clear field and the amount of bleeding profoundly impacts the ability of surgeons. Current study was designed to evaluate the effect of remifentanil combined with propofol versus Isoflurane on blood loss during ESS and its possible interaction with Depth of Anesthesia. Fifty one patients comprising 15 females and 36 males undergoing ESS were chosen for this study. One group received propofol and remifentanil to induce and maintain anesthesia and the second group received Isoflurane. Mean Arterial Blood Pressure (MAP), Depth of Anesthesia and total blood loss were recorded for the patients of both group. Data were analyzed using t-test, Repeated Measures ANOVA and Pearson’s correlation. P < 0.05 was considered statistically significant. Both agents induced hypotension during surgery. No significant difference was observed in total blood loss between two groups. DA was decreased in both groups, but no significant correlation was found between DA and MAP or DA and blood loss. There is no significant difference between remifentanil combined with propofol and Isoflurane in decreasing blood loss during ESS, thus we suggest usage of hypotensive anesthetic agent regardless of its type is ESS.