Objective To explore the effect of ultrasound‑guided transversus abdominis plane (TAP) block combined with opioid‑free anesthesia (OFA) on perioperative analgesic effect in patients undergoing total laparoscopic hysterectomy. Methods A total of 90 patients undergoing elective laparoscopic total hysterectomy were divided into two groups according to the random number table (n=45): an OFA group (group O) and a control group (group C). Patients in group T received ultrasound‑guided TAP block combined with OFA, while group C received general anesthesia by conventional opioid drugs. The heart rate and the mean arterial pressure (MAP) were recorded before surgery (T0), immediately after induction (T1), immediately after intubation (T2), 1 min (T3), 5 min (T4) and 20 min after pneumoperitoneum (T5), and at the end of surgery (T6). The postoperative eye‑opening time, time to extubation, the time of first off‑bed activity, and the time of first anal exhaust were recorded. The Numerical Rating Scale (NRS) scores in resting and active state and Ramsay sedation scores at postoperative 2, 6, 12, 24 h and 48 h were recorded. The rate of satisfaction with analgesia and adverse reactions within 48 h after surgery were also recorded. Results Compared with those at T0, the heart rate, MAP of group C and the MAP of group O significantly decreased at T1 (P<0.05), the heart rate, MAP of group C, the heart rate of group O significantly increased at T2 (P<0.05); the heart rate and MAP of group O at T1 were significantly higher than those of group C (P<0.05); there was no significant difference at other time points (P>0.05). Group O showed remarkable lower postoperative eye‑opening time, time to extubation, and time of first anal exhaust than group C (P<0.05), and there was no significant difference in the time of first off‑bed activity between the two groups (P>0.05). There was no significant difference in NRS score between the two groups at each time point (P>0.05). Group O presented significantly lower Ramsay's score than group C at postoperative 2 h (P<0.05), but there was no significant difference at other time points (P>0.05). There was also no significant difference in the rate of satisfaction with analgesia and adverse reactions within 48 h after surgery between the two groups (P>0.05). Conclusions Ultrasound‑guided TAP combined with OFA can exert good analgesic effect on patients undergoing laparoscopic total hysterectomy, with stable intraoperative hemodynamics and good recovery quality.