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Objective: To compare the effectiveness, adverse effects, and cost-effectiveness of percutaneous neurolytic celiac plexus block (NCPB) versus traditional medication strategies for the treatment of patients with advanced cancer having severe upper abdominal cancer pain., Methods: This retrospective study included 81 patients with advanced upper abdominal cancer admitted to The Sixth People's Hospital Affiliated to Shanghai Jiaotong University between January 2013 and July 2014. The patients were divided into percutaneous NCPB (treatment) and medication for pain (control) groups. The outcomes were measured in terms of Numeric Rating Scale (NRS) score and Karnofsky Performance Status (KPS) score before treatment and on the 3rd, 7th, 14th, and 28th days posttreatment. The effectiveness and cost-effectiveness of the therapy were assessed using analysis of the health economics., Results: The improvements in NRS score (1.42 ± 1.09 vs 4.03 ± 0.96, P < .01) and KPS score (65.55 ± 9.09 vs 63.03 ± 8.961, P < .01) in the treatment group were significantly superior compared to the control group on the 7th day of treatment, followed by no significant difference between the 2 groups on the 14th and the 28th day of treatment. Health economics evaluation revealed that the medicine-specific costs and total health care costs were significantly reduced in the treatment group compared to the control group ( P < .05), but no significant differences between the 2 groups ( P > .05) were seen in the costs of hospitalization, examinations, and treatment., Conclusion: The percutaneous NCPB method shows promising results and better cost-effectiveness for treating patients with advanced cancer having severe upper abdominal pain.