Background: Overview of post-operative pain control strategies lacks high quality effectiveness of the commonly used analgesics. Restricted use of strong systemic analgesics borne out of the fear of respiratory depression and other opoids related complications like nausea, vomiting, constipation, urinary retention etc. that results in failure to provide continuous analgesia of good quality in post-operative period. Therapeutic transdermal fentanyl (TTF) is a unique & innovative way of administering strong analgesic fentanyl transcutenously. Pharmacokinetic studies provides sufficient evidences that with TTF plateau analgesic concentration of fentanyl are attained after 8–12 hours and are maintained over prolonged period of 72 hours or more as the drug remains in circulation even after removal of patch. Therefore, TTF is expected to provide continuous analgesia of superior quality in post,operative period. Materials and Methods: 25 patients included in the study underwent major surgeries under uniform method of general anesthesia with gas, oxygen, relaxant and analgesic technique with controlled ventilation on Bain circuit. On these patients fentanyl transdermal patch releasing 50 mcg/hour fentanyl was applied to the hair free skin on lateral chest wall and secured in place just before induction of anesthesia. We assessed the quality, duration and intensity of pain; patient’s comfort score, requirements of rescue analgesics, efficacy & safety in its use, patient’s satisfaction. We vigilantly observed them for any adverse cardiovascular, respiratory and local complications. Results: 68% (17/25) patients did not demand rescue analgesic dose during entire post-operative period and mean VAS score was less than 1 after 12 hours post-operatively till the observation period of 72 hours. Only 32% (8/25) of the patients required supplement analgesic with one/two dose of 75 mg diclofenac sodium by intramuscular route. All patients expressed satisfaction with the analgesia provided; some had local complications like erythema at patch application site. The patients under study neither showed incidences of severe respiratory depression nor acute changes in cardiovascular parameter (HR, ECG and SBP, DBP) measurement throughout study period. The changes observed in cardiovascular and respiratory parameter were in-significant and did not require specific treatment. Conclusion: Therapeutic Transdermal Fentanyl releasing 50 mcg/hr fentanyl can be safely used to control post-operative pain and is effective after 8–12 hours of application with fewer side effects at patch application site.