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Introduction: Arthroscopy for knee surgery is the most often used minimally invasive orthopaedic surgical technique. Postoperative discomfort can be caused by irritation to the nerve endings in the synovial tissue, the fat pad in the front of the knee, and the joint capsule that can take place during the excision and resection. Aim: To compare the efficacy of Intra-Articular (IA) dexmedetomidine versus buprenorphine for postoperative analgesia following arthroscopic knee surgeries. Materials and Methods: A prospective interventional study was carried out for a period of one and a half years from January 2021 to June 2022 at Department of Anaesthesiology B.L.D.E. (Deemed to be University) Shri B.M. Patil Medical College, Hospital and Research Centre, Vijayapura, Karnataka, India. Around 80 patients of both genders of American Society of Anaesthesiologists (ASA) grade I and II who were scheduled for arthroscopic knee surgeries were randomly divided into two equal groups of 40 each. After the operation was finished, the patients in each group received the respective medications intra-articularly through an arthroscopy port. Group D received Inj. Dexmedetomidine 100 mcg+ Inj. Bupivacaine 0.25%, 20 mL. Injections of buprenorphine 100 mcg and bupivacaine at a concentration of 0.25%, 20 mL were given to the participants in group B. Immediately following surgery, the patient's temperature, pulse, Mean Arterial Pressure (MAP), and Visual Analogue Scale (VAS) score for pain were all monitored and recorded at the 1st, 2nd, 4th, 8th, 12th and 24th hour. Time to first rescue analgesia, the number of patients requiring rescue analgesia within the next 24 h, the visual analog scale at rest, and on mobilisation at 1st, 2nd, 4th, 8th, 12th, and 24 hour were measured. Side-effects like sedation, pruritis, nausea, vomiting, respiratory depression, and hypotension were also monitored. Descriptive statistics were reported as mean (SD) for continuous variables, and frequencies (percentage) for categorical variables. Data were statistically evaluated with IBM Statistical Package for the Social Sciences (SPSS) Statistics for Windows, Version 26.0, IBM Corp., Chicago, IL. Results: The mean age of the study participants was 38.38±11.30 years among the buprenorphine group and 36.40±12.07 years among the Dexmedetomidine group. Among the Buprenorphine group 52.5% were females and 47.5% were males. There was a statistically significant difference in VAS score at rest and mobilisation between the groups. The mean time for first rescue analgesia was longer for the buprenorphine group 1016.22±137.54 minutes and for the dexmedetomidine group, it was 523.67±117.47 minutes. Rescue analgesia was given to 9 (22.5%) in the buprenorphine and 18 (45%) in the dexmedetomidine group. Conclusion: In comparison to IA dexmedetomidine, buprenorphine produces analgesia for a longer period of time and reduces the amount of postoperative rescue analgesic that is required. [ABSTRACT FROM AUTHOR]