OBJECTIVE: The authors of this study sought to determine the outcomes of patients undergoing superficial peroneal nerve (SPN) release to treat lower-extremity pain and describe consistent anatomical landmarks to direct surgical planning. METHODS: This retrospective cohort study examined 54 patients with pain in the SPN distribution who were treated with decompression between 2011 and 2014. Patients rated pain and the effect of pain on quality of life (QOL) on the visual analog scale (VAS) from 0 to 10. Scores were then converted to percentages. Linear regression analysis was performed to assess the impact of the preoperative effect of pain on QOL, age, body mass index (BMI), and preoperative duration of pain on the postoperative effect of pain on QOL. Measurements were made intraoperatively in 13 patients to determine the landmarks for identifying the SPN. RESULTS A higher BMI was a negative predictor for improvement in the effect of pain on QOL. A decrease in pain compared with the initial level of pain suggested a nonlinear relationship between these variables. A minority of patients (7 of 16) with a preoperative pain VAS score ≤ 60 reported less pain after surgery. A large majority (30 of 36 patients) of those with a preoperative pain VAS score > 60 reported improvement. Intraoperative measurements demonstrated that the SPN was consistently found to be 5 ± 1.1, 5 ± 1.1, and 6 ± 1.2 cm lateral to the tibia at 10, 15, and 20 cm proximal to the lateral malleolus, respectively. CONCLUSIONS: A majority of patients with a preoperative pain VAS score > 60 showed a decrease in postoperative pain. A higher BMI was associated with less improvement in the effect of pain on QOL. This information can be useful when counseling patients on treatment options. Based on the intraoperative data, the authors found that the SPN can be located at reliable points in reference to the tibia and lateral malleolus. ©AANS, 2017.