Rationale and background: Perineural dexmedetomidine extends the duration of local anesthetic-induced peripheral nerve blocks in the experimental and the clinical settings. The effects of perineural dexmedetomidine on the pharmacodynamic profile of bupivacaine-induced femoral nerve block were not previously explored. We hypothesized that the addition of perineural dexmedetomidine will extend the duration of femoral nerve block in patients undergoing arthroscopic knee surgery. Patients and methods: This randomized, controlled double blinded study included 45 adult patients undergoing arthroscopic knee surgery. Ultrasound-guided femoral nerve block was initiated 30 min before induction of general anesthesia. Femoral nerve block was achieved with the use of 25 ml of bupivacaine 0.5% in all patients. Bupivacaine was combined with 0.5 ml normal saline (control group, n=15), 50 g (0.5 ml) perineural dexmedetomidine (n=15), or 50 g(0.5 ml) intramuscular dexmedetomidine (n=15). All patients received a standard general anaesthetic after ensuring successful femoral nerve block. The onset and duration of sensory and motor blocks, the time to first request to postoperative rescue analgesic, Richmond Agitation-Sedation Score, haemodynamic data, resting and dynamic visual analogue pain scores, were reported at predetermined time assessment points. Postoperative rescue intravenous morphine consumption over 24 hours was recorded. Results: The onset of sensory block was significantly shorter and its duration was extended with the use of perineural dexmedetomidine compared to the control and systemic route of administration. The onset of motor block was comparable in the three study groups. The duration of motor block was significantly longer in the perineural dexmedetomidine group. The time to first request to rescue analgesia was prolonged and total postoperative morphine consumption was reduced in the perineural dexmedetomidine group. Postoperative sedation was more encountered at the 30 min and two hours assessment points in the perineural and intramuscular dexmedetomidine groups. Statistically significant reductions in systolic blood pressure and heart rate were observed up to 45 minutes after induction of general anesthesia in all groups compared to the haemodynamic variables among the three study groups. Conclusion: The use of perineural dexmedetomidine as an adjuvant to bupivacaine reduces the onset and prolongs the duration of femoral nerve block in patients undergoing arthroscopic knee surgery.