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There is still debate regarding whether the surgical release of entrapped lower extremity nerves reduces complaints of associated neuropathy and results in gain of sensory function. The aim of this study was to investigate which factors are associated with a favorable surgical outcome, by follow-up of patients previously participating in a randomized controlled trial.The authors evaluated the 5-year follow-up of diabetic patients previously participating in the Lower Extremity Nerve Entrapment Study (LENS). Visual analogue pain scores, satisfaction, complaints, quality of life (i.e., 36-Question Short-Form Health Survey and EuroQol 5 Dimensions instrument), sensory function, and incident ulceration and amputation were assessed. Differences between patients who underwent unilateral versus bilateral decompressions were investigated.Thirty-one of the original 42 LENS participants were measured, of which eight patients underwent additional decompression of the contralateral leg, after 12-month LENS follow-up. At 5 years, bilateral surgical patients (n = 8) had significantly lower pain scores and higher quality of life compared with unilateral surgical patients (n = 23), were younger, had a lower age when diagnosed with diabetes, and had a lower body mass index at baseline. Pain scores of the additional decompressed leg decreased in a manner similar to that of the initial decompressed leg during follow-up. Patients with severe preoperative sensory loss did worse; 41.2 percent of the LENS Follow-Up Study subjects underwent or considered undergoing contralateral surgery.The authors’ results suggest that the beneficial effects of lower extremity nerve decompression surgery are reserved for a select group of patients, of which preoperative nerve damage, age, duration of diabetes, and body mass index are important effect modifiers.Therapeutic, III.