Background: This randomized, controlled study aimed to investigate the effect of general anesthesia plus epidural anesthesia on catheter-related bladder discomfort (CRBD) in patients who underwent abdominal operation with urinary catheterization.Methods: A total of 150 patients scheduled for abdominal operation under anesthesia with urinary catheterization were randomized to receive general anesthesia plus epidural anesthesia (N = 74, GA + EA group) or general anesthesia (N = 76, GA group). The occurrence and severity of CRBD, systolic blood pressure (SBP), diastolic blood pressure (DBP), and heart rate (HR) were recorded at 0 hour (h), 0.5, 1, and 3 h after tracheal extubation. Besides, postoperative adverse events were assessed.Results: The occurrence and severity of CRBD at 0, 0.5, 1, and 3 h were all reduced in GA + EA group compared to GA group (all P < 0.05). Meanwhile, subgroup analyses showed that the reduction of occurrence and severity of CRBD in GA + EA group compared to GA group was more obvious in male patients and patients ≥50 years. Besides, SBP at 0, 0.5, 1, and 3 h, as well as DBP at 0, 0.5, and 3 h were all decreased in GA + EA group compared to GA group (all P < 0.05), while HR was increased at 0 h in GA + EA group compared to GA group (P = 0.034). Moreover, the occurrence of pain, severity of pain and occurrence of vomiting were similar between GA + EA group and GA group (all P > 0.05).Conclusion: General anesthesia plus epidural anesthesia decreases CRBD occurrence and severity with tolerable safety compared with general anesthesia in patients who undergo abdominal operation with urinary catheterization.