Neurolytic celiac plexus block (NCPB) is claimed to be an effective method of pain control for pancreatic cancer pain. However, the factors that may influence long-term analgesia, adverse effects, and quality of life after performing NCPB have never been determined. In a prospective multicenter study, 22 patients who underwent NCPB were followed until death. Numerous parameters other than pain and symptom intensity were evaluated, including age, gender, initial site of cancer, sites of pain, possible peritoneal involvement, technique, and oncologic interventions. Indices were calculated to determine the opioid consumption ratio (EAS) and the trend of opioid escalation (OEI). NCPB was effective in reducing opioid consumption and gastrointestinal adverse effects for at least 4 weeks. In the last four weeks prior to death, there was the typical trend of increasing symptom intensity common to the terminal cancer population. None of the factors studied influenced the analgesic effectiveness of NPCB. NPCB, performed by skilled clinicians, regardless of the technique chosen, is a safe and useful means that should be considered as an adjuvant to common analgesic regimens at any stage, as it may allow the reduction of the visceral component of pancreatic pain that may prevail in certain phases of the illness. The analgesic and symptomatic effect of NCPB is presumably advantageous for about four weeks. A possible factor interfering with long-term outcome includes the capacity of cancer to involve the celiac axis, which can distort the anatomy and prevent neurolytic spread, or modify the pain mechanisms. Outcomes are strongly based on individual variation.