BACKGROUND: Peripheral neuromodulation is often used as chronic neuropathic pain treatment. Percutaneous electrical nerve stimulation (PENS) is generally utilized with several probes at the same time and repeated treatments. OBJECTIVES: Evaluate the short- and long-term efficacy of a single probe and single shot PENS approach. STUDY DESIGN: Multicenter, prospective, observational study. SETTING: Four Italian pain therapy centers. METHODS: Inclusion criteria were age = 18 and = 80 years, presence of severe peripheral neuropathic pain lasting more than 3 months, localized and refractory to pharmacological therapies. Patients with infection, coagulopathies, psychiatric disorders, pacemakers, or implantable cardiac defibrillators were excluded. PATIENTS: Seventy-six patients (47 women, 29 men), mean age 62 ± 14 years, affected by neuralgia (21 herpes zoster infection, 31 causalgia, 24 postoperative pain) were enrolled in the study. INTERVENTION: After localization of trigger point and/or allodynic/hyperalgesic area, PENS therapy was achieved with a single 21 gauge conductive probe tunneled percutaneously and a neurostimulator device. MEASUREMENT: Numerical Rating Scale (NRS) and Neuropathic Pain Scale (NPS) were assessed at baseline, 60 minutes after PENS, at one week, after one, 3, and 6 months; perceived health outcome was measured with Euroqol-5 dimension (EQ-5D) questionnaire at baseline and at 6 months. Adverse events and patient satisfaction were reported. RESULTS: NRS and NPS decreased significantly after 60 minutes and the reduction remained constant over time at follow-up. EQ-5D increased significantly with respect to the baseline. Two nonclinically significant adverse events (one contralateral dysestesia and one self-resolving hematoma) were observed. LIMITATIONS: Small sample size and non-randomized observational study; high prevalence of post-herpetic and occipital neuralgias. CONCLUSION: PENS therapy produced significant and long-lasting pain relief in chronic peripheral neuropathic pains of different etiology. The present study confirms the feasibility, safety, and repeatability of this minimally invasive technique.