Purpose The aim of this study was to investigate the efficacy of esmolol on intraoperative hemodynamic and perioperative analgesic management. Methods Totally, 125 patients undergoing colectomy were randomly divided into three groups. Group S (saline group) was administered 0.75 mL/kg/h of normal saline for 5 min before anesthesia induction and maintenance of 0.25 mL/kg/h; Group E 1 and Group E 2 were administered 0.5 mg/kg and 1.0 mg/kg esmolol for 5 min before anesthesia induction, and maintained of 0.5 mg/kg/h and 2.0 mg/kg/h, respectively. Several parameters including indexes of hemodynamics variation (primary outcome), intra- and postoperative analgesic usage, and pain score were measured. Results Group E 1 and Group E 2 had significantly lower intubation response than Group S (P = 0.007, P = 0.001), and extubation response of Group E 2 was significantly lower than Group S (P = 0.007). The opioid consumption in Group E 1 and Group E 2 was significantly lower than in Group S intraoperatively (P = 0.020 and 0.007). The incidence of postoperative adverse reactions among the three groups was not statistically significant (P = 0.368 and 0.772). Conclusion Esmolol 0.5 mg/kg and 1.0 mg/kg infusion before intubation both can effectively inhibit the intubation response, while only maintenance with 2.0 mg/kg/h of esmolol can reduce the incidence of extubation response. At the same time, esmolol can decrease intraoperative opioid requirement without increasing the risk of adverse reactions. Trial Registration ChiCTR1900024538 and the date of registration was July 15, 2019 at http://www.chictr.org.cn .