This noninterventional, prospective study investigated the administration of tapentadol prolonged release (PR; the dosage form described in this article is commercially available in Germany as Palexia retard; Grünenthal GmbH, Aachen) for severe chronic pain in routine clinical practice over a 3-month period. Effectiveness analyses included data from 3134 patients; 1331 received World Health Organization (WHO) Step III pretreatment. A total of 97.8% of patients received long-term analgesic pretreatment (42.5% with strong opioids). Switching to tapentadol PR produced a 3.9-point mean pain reduction (baseline, 7.0 ± 1.5; end of observation, 3.1 ± 1.8; 11-point numerical rating scale; descriptive P value ≤.001); 72.1% of patients experienced clinically relevant pain relief (≥50%) at the end of observation. Significant decreases in pain-related impairment of daily activities and improvements in quality of life (descriptive P value ≤.001) were observed with tapentadol PR with good tolerability. Tapentadol PR was effective for various pain indications in patients previously receiving strong opioids (67.2% achieved clinically relevant pain relief). Tapentadol PR can be considered an alternative therapy to classical opioids for treatment of severe chronic pain.