Abstract: Background & Aims: Celiac plexus neurolysis is an elegant way of reducing pain in patients with pancreatic cancer. The aim of this work was to compare the effectiveness of ultrasound versus fluoroscopy-guided celiac plexus neurolysis in pancreatic cancer management. Patients and Methods: This study included 60 patients presenting with pancreatic cancer pain; who were subjected to one session of celiac plexus neurolysis and were divided equally into two groups: - Group (1): included 30 patients (12 females&18 males); who were exposed to ultrasound (US)-guided celiac plexus neurolysis and group (2): included 30 patients (10 females& 20 males) who were exposed to fluoroscopy-guided celiac plexus neurolysis. Abdominal pain was assisted by visual analogue score (VAS). Results: Regarding VAS, our results revealed that all patients showed improvement after celiac plexus neurolysis either through ultrasound technique or via percutaneous fluoroscopy technique. Furthermore, the ultrasound group recorded more significant pain relief with improved VAS than the fluoroscopy group immediately and on long-term follow-up with mean ± SD as follows: - Immediately (9.2±0.8) to (2.5 ± 0.7) vs (9.1±0.7) to (3.5 ± 0.82, respectively) ; After 1 week (1.1 ± 0.8 vs. 3.6 ± 1.7, respectively), after 1 month ( 1 ± 0.9 vs. 3.7 ± 1.9), after three months (1.7 ± 1.01 vs. 5.9 ± 1.7, respectively) and after 6 months (2.3 ± 0.6 vs. 7.5 ± 1.6, respectively). Conclusion: The study revealed that ultrasound-guided celiac plexus neurolysis is more durable, tolerable, effective and safe compared to fluoroscopy-guided neurolysis of patient suffering from pancreatic cancer pain.