Introduction: Intraabdominal CO2 gas after laparoscopic cholecystectomy causes postoperative shoulder-tip pain. Many methods of analgesia have been used to reduce this pain, including analgesic drugs, intraperitoneal local anesthetic, intraperitoneal saline, a gas drain, heated gas, low-pressure gas, and nitrous oxide pneumoperitoneum. The aim of this study was to evaluate the efficacy of combined low-pressure CO2 pneumoperitoneum and intraperitoneal infusion of normal saline in reducing the incidence of postoperative shoulder-tip pain. Methods: Altogether, 109 patients undergoing elective laparoscopic cholecystectomy were randomized prospectively into three groups. Patients in group A (n = 34) underwent laparoscopic cholecystectomy with 14 mmHg CO2 pneumoperitoneum; patients in group B (n = 37) underwent laparoscopic cholecystectomy with 10 mmHg CO2 pneumoperitoneum; and those in group C (n = 38) underwent laparoscopic cholecystectomy with 10 mmHg CO2 pneumoperitoneum in addition to intraperitoneal normal saline infusion in the right hemidiaphragmatic area. Shoulder-tip pain was recorded on a verbal rating scale 2, 6, 12, 24, and 48 hours after operation. Results: Twelve patients in group A (35.2 percent), six in group B (16.2 percent), and seven in group C (18.4 percent) complained of shoulder-tip pain. Hence, there was a significant decrease in the frequency of shoulder-tip pain in groups B and C in relation to group A, but there was no significant difference between groups B and C. The postoperative shoulder-tip pain scores were significantly reduced in group C at 6, 12, and 24 hours. The number of patients who required additional analgesics was also reduced in group C. Conclusions: Low-pressure CO2 pneumoperitoneum reduces the number of patients complaining of shoulder-tip pain and the intensity of the pain after laparoscopic cholecystectomy. The addition of intraperitoneal normal saline infusion to low-pressure CO2 pneumoperitoneum seems to reduce the intensity but not the frequency of shoulder-tip pain after laparoscopic cholecystectomy.