Objective: To compare the clinical efficacy of using ultrasonic scalpel (US) versus monopolar electroscalpel (MES) in open radical operation for colorectal cancer. Methods: Sixty-two patients with colorectal cancer admitted to our hospital during the same period of time were randomly assigned to undergo radical operation by using either US (30 cases) or MES (32 cases) approach and then the effectiveness of the two approaches was compared. Results: The mean incision length of US group and MES group were (6±2) cm, (15±4) cm; and the mean operative blood loss were (50±6) mL, (150±30) mL, respectively, both of the indexes had significant differences (both P＜0.05). The mean operation time and the mean number of lymphoid node dissected of US group and control group were (130±25) min, (145±30) min, and 13±6, 12±5 respectively, and both of the indexes had no significant difference (both P＞0.05). The time for use of postoperative analgesics, anal gas passage and hospital stay, and the mean postoperative drainage volume of the US group were all better then those of the MES group (all P＜0.05). No significant difference was noted between the two groups in incidence of postoperative complications (all P＞0.05). Conclusions: The use of US in open radical resection for colorectal cancer is better than that of MES, because it has the advantages of minimal trauma and quick recovery after surgeny.