Background: Postoperative pain control remains unsatisfactory. Patients who underwent laparotomy may have moderate to severe acute postoperative pain. Comparative cost-effectiveness of the following postoperative pain treatment options remains to be investigated: patient-controlled intravenous analgesia (PCIA) with flurbiprofen therapy, flurbiprofen monotherapy, parecoxib monotherapy, or dezocine monotherapy. Aim: To provide a cost-effectiveness analysis (CEA) of four analgesic regimens for patients with postoperative pain following laparotomy surgeries. Method: Patients with postoperative pain following laparotomy were retrospectively reviewed from a postoperative pain management database created by pharmacists, and divided into four groups according to analgesic regimens. The clinical outcomes were visual analogue scale (VAS) scores and the incidence of adverse drug events. The CEA was conducted by developing a decision tree model based on retrospective data. The maximum incremental cost-effectiveness ratio (ICER) of the four regimens was used as the willingness-to-pay (WTP) value. Meanwhile, the uncertainty of the base-case results was examined by one-way and probabilistic sensitivity analyses. Results: A total of 677 patients were included in the retrospective study. PCIA with flurbiprofen therapy had the lowest VAS scores at 6, 24, 48 h postoperatively. Based on the base-case results, PCIA plus flurbiprofen was the optimal regimen with the highest effectiveness, while flurbiprofen monotherapy had the lowest cost. PCIA plus flurbiprofen was the optimal regimen even with a WTP value of 0 dollars. Conclusion: PCIA plus flurbiprofen therapy was the optimal regimen. Parecoxib monotherapy was more cost-effective than flurbiprofen monotherapy. The findings may guide the selection of postoperative pain management.