Background: This Study was designed to comparatively evaluate the postoperative analgesia efficacy of levobupivacaine 0.5% in combination with dexmedetomidine and fentanyl in wound infiltration technique following open cholecystectomy surgeries. Methodology: After ethical committee, approval, a double blind randomized controlled study was conducted on 100 patients, divided into 2 equal groups (n=50) by using computer generated random number table (considering 5% alpha error of 80% power of study), ASA grade I & II, 18 to 60 years age scheduled for open cholecystectomy surgeries over 1year duration. A standard general anaesthetic technique was used and all patients received wound infiltration at the time of wound closure. Group D received 0.5% Levobupivacaine with injection Dexmedetomidine (1mcg/Kg) and 0.9% normal saline while Group F received 0.5% Levobupivacaine with injection Fentanyl (1mcg/Kg) and 0.9% normal saline. Total volume of solution was made 25 ml. Postoperative rescue analgesia was provided with Injection Tramadol (1mg/Kg) when VAS score >3. Mean between the 2 groups were compared using independent t-test and variance between the groups by Chi-square test.