Objective To evaluate the safety of dexmedetomidine (Dex) for sedation and analgesia for patients undergoing percutaneous transforaminal endoscopic discectomy (PTED) in prone position under close monitoring and its effect on assisting local infiltration anesthesia. Methods A total of 120 patients scheduled for PTED were divided into three groups (n=40), according to random number table method: low dose Dex group (D1 group, loading dose 1 µg/kg for 10 min, followed by 0.3 µg·kg−1·h−1), higher dose Dex group (D2 group, loading dose 1 µg/kg for 10 min, followed by 0.5 µg·kg−1·h−1) and a normal saline group (C group, 1.5 ml·kg−1·h−1 for 10 min, followed by 0.125 ml·kg−1·h−1). Heart rate, mean arterial pressure (MAP), pulse oxygen saturation (SpO2) and bispectral index (BIS) were recorded at each time point such as before sedation (T0), at the beginning of the operation (T1), during grinding the articular process with a trephine (T2) and at the end of the operation (T3). The operative time, lidocaine dosage and crystalloid fluid input were recorded at T3, and the Visual Analogue Scale (VAS) scores, Ramsay Sedation Scale and incidence of pain were recorded at T2. Results At T1, T2 and T3, compared with C group, the heart rate, MAP and BIS in D1 and D2 groups were significantly lower (P<0.05), while compared with D1 group, the heart rate in the D2 group further decreased (P<0.05). At T1, the MAP in the D2 group was significantly lower than that in the D1 group (P<0.05). Compared with C group, the lidocaine dosage, VAS score and the incidence of pain in the D1 and D2 groups were significantly lower, while Ramsay Sedation Scale was significantly increased (P<0.05). Compared with D1 group, the VAS score and the incidence of pain in the D2 group were significantly higher (P<0.05). Conclusions Dex can effectively and safely relieve pain and anxiety in PTED patients and reduce the use of local anesthetics in prone position under close anesthesia monitoring.