Low back pain (LBP) is a highly prevalent chronic pain condition with a neuropathic component of pain that limits the benefits of classical opioids. Tapentadol is an innovative drug for the treatment of chronic severe pain, with a dual mechanism of action combining µ-opioid receptors agonism and noradrenaline re-uptake inhibition (NRI). Its efficacy is equal to that of strong opioids, with a better tolerability profile and a consequently lower risk of treatment discontinuation. The aim of this study was to evaluate the analgesic efficacy and tolerability of tapentadol prolonged release (PR) vs. other analgesics in patients with moderate-to-severe neuropathic low back pain, before and after back surgery. The primary endpoints of the study were the rate of response to treatment, measured as ≥30% reduction in pain intensity on the Numeric Rating Scale (NRS), and tapentadol PR efficacy for pain relief. The secondary endpoints were the improvements of the neuropathic component of pain and of sleep quality. A total of 40 patients were enrolled in the study, receiving either tapentadol PR (n=21, 52.5%) or other analgesics (n=19, 47.5%), both before and after surgery. The rate of response to treatment was statistically in favor of tapentadol PR (p<0.01). The reduction in pain intensity was statistically significant in the group treated with tapentadol PR, both before and after surgery (p<0.01), with a complete resolution of pain 90 days after surgery. The quality of sleep after surgery improved more in patients treated with tapentadol PR than in the comparator group (p<0.01), with 100% of the patients reporting a "good" sleep quality 2 months after surgery. Tapentadol PR was well tolerated by all patients, and its efficacy for pain relief was also confirmed in our small group of "real-life" patients with chronic, severe low back pain. Overall, the tolerability of this treatment may help to improve patients' quality of life, which is frequently compromised because of pain and its related comorbidities.