Objective To explore the effect of opioid‑free anesthesia (OFA) on nausea and vomiting and recovery quality of patients after laparoscopic cholecystectomy (LC). Methods According to the random number table method, 99 patients who underwent elective laparoscopic cholecystectomy were divided into two groups: an control group (OA group) (n=50) and an OFA group (n=49). In the OA group, anesthesia was inducted with sufentanil and other drugs and maintained with remifentanil combined with sevoflurane. In contrast, esketamine was used for anesthesia induction in the OFA group, followed by anesthesia maintenance with esketamine combined with sevoflurane. Then, the incidence of nausea and vomiting [postoperative nausea and vomiting (PONV)] and other adverse reactions within 24 h after operation, the 40‑items Quality of Recovery Scale (QoR‑40) scores before surgery and at postoperative 24 h, 48 h and 7 d were recorded; the hemodynamics [mean arterial pressure (MAP), and heart rate] at each point of the operation [at admission (T1), 1 min after intubation (T2), at the beginning of the operation (T3), at the time of pulling the gallbladder (T4), and at the end of the operation (T5)] were recorded, anesthesia and intraoperative data were recorded in the two groups. Results Compared with the OA group, the OFA group showed decreases in the incidences of PONV, vomiting, abdominal distension and intraoperative phenylephrine consumption within postoperative 24 h, heart rate at T3‒T5, and MAP at T2‒T5 (all P<0.05); reduction in the length of post-anesthesia care unit (PACU) stay (P<0.05); and increases in physical comfort, physical self‑care, and pain scores within postoperative 24 h, and QoR‑40 scores, their emotional state and physical comfort scores at postoperative 48 h (all P<0.05). Compared with those before surgery, patients in both groups presented decreases in QoR‑40 scores, physical comfort and pain scores at postoperative 24 h and 48 h (all P<0.05); decreases in emotional state and physical self‑care scores at postoperative 24 h (all P<0.05); and increases in QoR‑40 scores, emotional state and pain scores at postoperative 7 day (all P<0.05). The differences in the remaining indicators were not statistically significant (all P>0.05). Conclusions OFA can reduce the incidence of PONV, vomiting and abdominal distension within 24 h after LC, and provide better hemodynamic stability. It is statistically but not clinically significant in improving the quality of patients' postoperative recovery.