Purpose Laparoscopic cholecystectomy (LC) is the definitive treatment for symptomatic gallstone disease, however the indications for surgical management of biliary pain with gallstone negative ultrasound are less clear. This study sought to investigate the post-operative outcomes of patients following LC for clinically suspicious biliary pains yet with acalculous ultrasound, focusing on symptom improvement and surgical safety. Methods This study involved a retrospective analysis of a single-surgeon’s 10-year database of public and private patients undergoing LC for biliary pain with acalculous ultrasound. Acute admissions, chronic pain syndromes or major concurrent surgery were excluded. Primary outcome measures were biliary-type pain resolution 3 months post surgery (complete, partial, none), with secondary outcomes focusing on surgical safety measures: post-operative wound infection, bile leak, length of stay, returns to theatre and 30-day readmissions. Results 736 LCs were performed acutely and electively from 2015 to 2024 inclusive by a single surgeon. 110 LCs were performed on patients with no gallstones reported on ultrasound. Notably, 21 patients were subsequently found to have gallbladder calculi, thereby representing false negative ultrasound reports. Another 89 patients were confirmed to be acalculous at surgery or on histology report however 20 did not meet study inclusion criteria, leaving 69 eligible patients. There were 82% complete, 12% partial and 6% non-responders at 3 months. The average length of stay was 0.54 nights with no bile leak, wound infection or 30-day readmissions for these patients. Conclusion Ultrasound is the first line of imaging for suspected biliary pain, but false negative reports and acalculous biliary pain should also be considered when deciding to undergo laparoscopic cholecystectomy for pain management.