BACKGROUND Postlaparoscopic shoulder pain (PLSP) frequently occurs after various laparoscopic surgical procedures. Its mechanism is commonly assumed to be overstretching of the diaphragmatic muscle fibers due to the pressure of a pneumoperitoneum, which causes phrenic nerve-mediated referred pain to the shoulder. Based on this hypothesis, we speculated that during inspiration, the lung could squeeze out the phrenic nerve with carbon dioxide gas against the constantly pressurized abdominal cavity with increasing tidal volume (V(T)). Thus, we examined whether mechanical ventilation with a low V(T) (LTV, V(T) 7 ml/kg) during a pneumoperitoneum might reduce PLSP in patients undergoing laparoscopic appendectomy compared with ventilation with the traditional V(T) (TTV, V(T) 10 ml/kg). METHODS In a prospective trial, 64 adult patients undergoing laparoscopic appendectomy were randomly assigned to two groups of 32 each (LTV and TTV groups). Intravenous ketorolac was used as a postoperative rescue analgesic. The 2-, 4-, 24-, and 48-h postoperative incidence and severity of PLSP, severity of surgical pain, and need for rescue analgesia was assessed. RESULTS The overall incidence of PLSP was similar in both groups (57.1% in the LTV group vs. 65.5% in the TTV group). Compared with the TTV group, the incidence and PLSP verbal rating scale (VRS) did not decrease in the LTV group throughout the study period. No statistically significant differences were observed in the VRS surgical pain score, the cumulative ketorolac consumption at each time point, or the time to first rescue analgesia. CONCLUSIONS Mechanical ventilation with a reduced 7 ml/kg V(T) during a pneumoperitoneum does not reduce the frequency and severity of PLSP after laparoscopic appendectomy compared with ventilation with the traditional V(T) (10 ml/kg).