Background: Peripheral nerve decompression surgery has been reported to be effective for pain reduction in patients with painful diabetic peripheral neuropathy. The aim of this study was to characterize which patients may have more pain relief benefits in the lower limbs after nerve decompression surgery. Methods: A retrospective study was conducted. Pain levels were measured with the Numerical Rating Scale. Treatment effects were classified by either substantial relief (at least 50 percent reduction in Numerical Rating Scale score compared with preoperative Numerical Rating Scale score) or nonsubstantial relief (<50 percent reduction or worse in Numerical Rating Scale score) at 12 months based on established criteria. Sex, age, body mass index, duration of diabetes mellitus, duration of diabetic peripheral neuropathy pain, preoperative Numerical Rating Scale score, and two-point discrimination were evaluated using univariate and logistic regression analysis. Results: The mean preoperative Numerical Rating Scale score (8.65 1.29) decreased significantly 6 days (3.56 2.22; p < 0.01), 6 months (3.03 +/- 2.11; p < 0.01), and 12 months (3.44 +/- 2.36; p < 0.01) after surgery; 64.7 percent of patients had substantial pain relief at 12 months. According to univariate and logistic regression analysis, better two-point discrimination was associated with substantial pain relief (OR, 3.700; p = 0.046, logistic regression analysis). Conclusions: Nerve decompression surgery was able to alleviate pain in patients with painful diabetic peripheral neuropathy. Two-point discrimination may be a predictive factor for the prognosis of painful diabetic peripheral neuropathy after nerve decompression surgery. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.