PURPOSE: Transversus abdominis plane (TAP) block is a safe, effective, and promising analgesic procedure, but TAP block only cannot overcome postoperative pain. We conducted a prospective randomized study to evaluate postoperative pain control using multimodal analgesia (MA) combined with a single injection TAP block compared with epidural analgesia (EA) after laparoscopic colon cancer surgery. METHODS: Sixty-seven patients scheduled for elective laparoscopic colon cancer surgery were enrolled in this study and randomized into EA and MA groups. The primary endpoint was the frequency of additional analgesic use until postoperative day (POD) 2. The VAS score, blood pressure, time to bowel movement, time to mobilization, postoperative complications, and length of hospital stay were also compared between the two groups. RESULTS: Sixty-four patients (EA group, n = 33; MA group, n = 31) were analyzed. The patient characteristics did not differ markedly between the two groups. The frequency of additional analgesic use was significantly lower in the MA group than in the EA group (P < 0.001), whereas the VAS score did not differ markedly between the two groups. The postoperative blood pressure on the day of surgery was significantly lower in the MA group than in the EA group (P = 0.016), whereas urinary retention was significantly higher in the EA group than in the MA group (P < 0.001). CONCLUSION: MA combined with a single injection TAP block after laparoscopic colon cancer surgery may be comparable to EA in terms of analgesia and superior to EA in terms of urinary retention.