BACKGROUND: This study was designed to measure in vivo effects of propofol, isoflurane and sevoflurane on apoptosis by measuring caspase-3 and tumor necrosis factor (TNF)-related apoptosis inducing ligand (TRAIL) blood level as apoptotic markers. METHODS: After obtaining ethical committee approval and informed written consents, sixty adult patients ASA I scheduled for open cholecystectomy participated in this study. They were randomally allocated into one of three equal groups to receive propofol infusion, low-flow isoflurane or sevoflurane for maintenance of anesthesia. Venous blood samples were collected preoperatively, immediately postoperative and after 24 hours to measure hemoglobin, hematocrit, creatinine, liver enzymes, serum TRAIL and caspase-3 levels. RESULTS: There was no significant difference in hematological markers and serum creatinine. Liver enzymes showed significant postoperative rise (P < 0.05). In Propofol group, TRAIL and caspase-3 levels were significantly elevated immediately postoperative then decreased significantly after 24-hours (P < 0.05). In Isoflurane group, immediate postoperative level of TRAIL was significantly higher than 24 hours reading and significantly lower than its level in Propofol group at the same timing meanwhile caspase-3 levels were comparable at different timings. In Sevoflurane group, TRAIL and caspase-3 levels increased significantly in both postoperative samples than preoperative level and than those of Isoflurane and Propofol groups after 24 hours concerning TRAIL (P & 0.05). CONCLUSIONS: This study concluded that isoflurane is superior and sevoflurane is the least effective among the three anesthetics in protection against apoptosis. This study neither proved nor excluded propofol-induced apoptosis. Further studies are required during lengthy procedure and in compromised patients.