Myofascial pain syndrome (MPS) of the trapezius muscle (TM) is a frequently occurring musculoskeletal disorder. However, the treatment of MPS of the TM remains a challenge. We investigated the effects of ultrasound (US)-guided pulsed radiofrequency (PRF) stimulation on the interfascial area of the TM. In addition, we compared its effect with that of interfascial block (IFB) with 10 mL of 0.6% lidocaine on the interfascial area of the TM. Thirty-six patients with MPS of the TM were included and randomly assigned into 2 groups. Eighteen patients underwent PRF stimulation on the interfascial area of the TM (PRF group) and 18 patients underwent IFB with lidocaine on the same area (IFB group). Pain intensity was evaluated using a numerical rating scale (NRS) at pretreatment, 2, 4, and 8 weeks after treatment. At pretreatment and 8 weeks after treatment, quality of life was assessed using the Short Form-36 Health Survey (SF-36), which includes the physical component score (PCS) and the mental component score (MCS). One patient in the PRF group was lost to follow-up. Patients in both groups showed a significant decrease in NRS scores at 2, 4, and 8 weeks after treatments and a significant increase in PCS and MCS of the SF-36 at 8 weeks after treatments. Two weeks after each treatment, the decrements of NRS scores were not significantly different between the 2 groups. However, 4 and 8 weeks after the procedures, we found that the NRS score was significantly lower in the PRF group than in the IFB group. At 8 weeks after the treatments, PCS and MCS of the SF-36 in the PRF group were significantly higher than those in the IFB group. For the management of MPS of the TM, US-guided interfascial PRF had a better long-term effect on reducing the pain and the quality of life compared to US-guided IFB. Therefore, we think US-guided PRF stimulation on the interfascial area of the TM can be a beneficial alternative to manage the pain following MPS of the TM.