Background Colorectal cancer is quite common, and surgery is the most effective treatment for most patients. However, postoperative pain management is generally inadequate in most patients. This study aimed to determine the effect of ultrasonography (USG)-guided preemptive erector spina plan block (ESPB), as part of multimodal analgesia, on postoperative analgesia in patients undergoing colorectal cancer surgery.  Methods This is a prospective, randomized, single-blind trial. This study included 60 patients (ASA I-II) who underwent colorectal surgery at the hospital of Ondokuz Mayis University. The patients were divided into the ESP group and control group. Intraoperatively, all patients were administered intravenous tenoxicam (20 mg) and paracetamol (1 g) as part of multimodal analgesia. Intravenous morphine via patient-controlled analgesia was administered in all groups postoperatively. The primary outcome was the total morphine consumption in the first 24 h after surgery. The secondary outcomes included visual analog scale pain scores at rest and coughing and deep inspiration in the first 24 h and at 3 months postoperatively; number of patients requesting rescue analgesia; incidence of nausea and vomiting and need for antiemetics; intraoperative remifentanil consumption; postoperative first oral intake; time to first urination, first defecation, and first mobilization; hospitalization time; and incidence of pruritus. Results Morphine consumption in the first 6 h postoperatively, total amount of morphine consumed in the first 24 h postoperatively, pain scores, intraoperative remifentanil consumption, incidence of pruritus, and postoperative antiemetic requirement were lower in the ESP group than in the control group. First defecation time and hospitalization time were shorter in the block group. Conclusions As a part of multimodal analgesia, ESPB reduced postoperative opioid consumption and pain scores in the early postoperative period and in the 3rd month.