Aim: To prove the safety and efficacy of endoluminal forceps biopsy during initial drainage and demonstrate its benefits for patients and physicians. Methods: From 2006, 101 consecutive patients with malignant biliary stenosis were enrolled in the analysis. All patients underwent percutaneous transhepatic biliary drainage (PTD) procedure and endoluminal forceps biopsy to obtain histological verification of stenosis. Seventy-six patients underwent biopsy 1–119 days after the drainage procedure (7.5F biopsy forceps). Twenty-seven patients underwent percutaneous drainage and biopsy in a single, combined procedure (5.2F disposable biopsy forceps). Results: Interventions with the single-procedure PTD biopsy were not associated with a higher rate of complications. The cumulative success rates of endoluminal biopsy in both groups were 77.6% and 81.5%, respectively. The average times needed to obtain a conclusive biopsy specimen from the time of initial drainage were 42 days and 11 days, respectively (p < 0.001). Patients undergoing endoluminal biopsy with the 5.2F forceps benefited from 1.2 fewer percutaneous interventions on average (p < 0.001). Conclusion: Percutaneous forceps biopsy is a safe procedure even when performed during initial drainage. Its success rate is comparable to that of the postponed biopsy procedure while malignancy is proven significantly sooner.