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Background and Aims: Total knee replacement (TKR) patients experience considerable post-operative pain. We evaluated whether addition of perineural dexmedetomidine to ropivacaine 0.2% in the femoral nerve block would enhance post-operative analgesia in patients undergoing unilateral TKR under spinal anaesthesia. Methods: Fifty patients were allocated randomly to two groups of 25 each. Group D received ropivacaine (0.2%) with dexmedetomidine (1.5 μg/kg), and Group C received ropivacaine (0.2%) with normal saline. Pain scores, time to the first request for analgesia and total consumption of ropivacaine in 48 h, along with haemodynamic parameters and sedation scores, were recorded. Quantitative data were compared using t-test, categorical data using Chi-square or Fisher's exact test and time variables using ANOVA. Results: The mean pain scores were significantly low till 2 h post-operatively in Group D. Time to the first demand for analgesia after initial loading dose was statistically prolonged in Group D, with mean duration of 346.8 ± 240 min, compared to 150 ± 115.2 min in Group C (P = 0.001). Total local anaesthetic consumption was also decreased over 24 and 48 h in Group D (P = 0.001). Haemodynamically, there was no significant variation in heart rate from their baseline mean values in either group (P > 0.05). However, the drop in systolic and mean blood pressure post-surgery was significant till 4 (P = 0.002) and 8 h (P = 0.02), respectively, in Group D. Group D patients were also significantly more sedated till 4 h post-operatively (P < 0.005). Conclusion: Adding dexmedetomidine to ropivacaine 0.2% in the femoral nerve block in patients undergoing unilateral TKR improves the quality and prolongs the duration of post-operative analgesia.