Background: There is no truly optimal treatment to cure refractory neuralgia of the infraorbital nerve. Recently, nondestructive pulsed radiofrequency (PRF) has become one of the most attractive interventional techniques for painful disorders. However, use of the technique for infraorbital neuralgia has been seldom reported. Objective: The purpose of this prospective study is to observe the effectiveness and safety of PRF treatment for neuralgia of the infraorbital nerve. Study Design: Prospective case series clinical outcome study. Setting: University Medical Center, Beijing, China Methods: From January 2011 to November 2012, 36 consecutive patients, following ineffective conservative therapy, underwent PRF treatment and completed 2-year follow-up. Numeric rating scales (NRS), effective rate, additional carbamazepine dosage, and side effects were recorded at postoperative day one, week one, week 2, month one, month 3, month 6, year one, and year 2. Patients were divided into effective group and ineffective group based on postoperative one -month total pain relief or more than 50% reduction in NRS and patients were satisfied with the effect, and possible factors affecting efficacy were compared between the 2 groups. Results: Effective rates were 69%, 69%, 64%, 50%, and 50% at postoperative month one, month 3, month 6, year one, and year 2, respectively. No serious side effects were observed, except that 9 patients felt short-term (one -month duration) mild numbness. Output voltage and tissue resistance in the effective group were significantly higher than the ineffective group (P < 0.01). Intraoperative output voltage was negatively correlated with postoperative one -month NRS (r = -0.332, P < 0.05). Limitations: The non-controlled and single-centered design of the study. Conclusions: Results demonstrated PRF treatment under computed tomography (CT) guidance for infraorbital neuralgia is safe, effective, and is expected to become an alternative for patients experiencing ineffective conservative therapy. Increasing the output voltage of PRF could be the chosen method to improve the efficacy.