Although endoscopic ultrasound-guided celiac neurolysis (EUS-CN) and percutaneous celiac neurolysis (PCN) are utilized to manage intractable pain in pancreatic cancer patients, no direct comparison has been made between the two methods. We compared the efficacy and safety of EUS-CN and PCN in managing intractable pain in such patients. Sixty pancreatic cancer patients with intractable pain were randomly assigned to EUS-CN (n = 30) or PCN (n = 30). The primary outcomes were pain reduction in numerical rating scale (NRS) and opioid requirement reduction. Secondary outcomes were: successful pain response (NRS decrease ≥50% or ≥3-point reduction from baseline); quality of life; patient satisfaction; adverse events; and survival rate at 3 months postintervention. Both groups reported sustained decreases in pain scores up to 3 months postintervention (mean reductions in abdominal pain: 0.9 (95% confidence interval (CI): −0.8 to 4.2) and 1.7 (95% CI: −0.3 to 2.1); back pain: 1.3 (95% CI: −0.9 to 3.4) and 2.5 (95% CI: −0.2 to 5.2) in EUS-CN, and PCN groups, respectively). The differences in mean pain scores between the two groups at baseline and 3 months were −0.5 (p = 0.46) and −1.4 (p = 0.11) for abdominal pain and 0.1 (p = 0.85) and −0.9 (p = 0.31) for back pain in favor of PCN. No significant differences were noted in opioid requirement reduction and other outcomes. EUS-CN and PCN were similarly effective and safe in managing intractable pain in pancreatic cancer patients. Either methods may be used depending on the resources and expertise of each institution.