Introduction Despite widespread adoption by the surgical community, high-quality prospective data supporting the practice of laparoscopic cholecystectomy (LC) for the treatment of biliary dyskinesia (BD) is lacking. Methods Adult patients meeting criteria for diagnosis of BD (Rome III symptoms, normal ultrasound, gallbladder ejection fraction<38%) were randomized to either LC or a trial of non-operative (NO) therapy with a low-dose neuromodulator (amitriptyline 25mg/day). Patients in the NO arm were allowed to cross over to the surgical arm and remain in the study for any reason. Besides collection of basic demographics and medical/surgical history, patients were administered a standardized quality of life (QOL) assessment (SF-8) and a symptom-specific questionnaire (Rome III criteria) at enrollment and monthly through the study to assess the effect of treatment on biliary symptoms and overall QOL. Results Thirty patients were enrolled over 12 months (15LC, 15NO). In the LC group, 13 underwent LC, 1 refused surgery, 1 withdrew. In the NO group, 14 crossed over to the LC group (of which 13 had LC), yielding 26 patients who underwent LC. SF-8 physical scores (PCS-8) were significantly improved at both the first and last follow-up visits (p<0.0001, p=0.0003 respectively). SF-8 mental scores (MCS-8) were also significantly improved at both the first and last follow-up visits (p=0.0187, p=0.0017 respectively). With median follow-up of 12 months [range 3–14], all 26 reported relief of pain. Conclusions This pilot study raises doubts regarding the feasibility of a randomized trial, presumably due to both clinician and patient bias toward LC and the lack of “gold-standard” non-operative treatments. However, these prospective data indicate that, with careful patient selection (standardized symptom criteria/imaging methodology), LC results in pain relief and significant improvement in QOL in BD patients. Further prospective study of these findings is warranted.