BACKGROUND & AIMS: Patients with diarrhea-predominant irritable bowel syndrome (IBS-D) anecdotally report symptom improvement after initiating a very low-carbohydrate diet (VLCD). This study prospectively evaluated a VLCD in IBS-D. METHODS: Participants with moderate to severe IBS-D were provided a 2-week standard diet, then 4 weeks of a VLCD (20 g carbohydrates/d). A responder was defined as having adequate relief of gastrointestinal symptoms for 2 or more weeks during the VLCD. Changes in abdominal pain, stool habits, and quality of life also were measured. RESULTS: Of the 17 participants enrolled, 13 completed the study and all met the responder definition, with 10 (77%) reporting adequate relief for all 4 VLCD weeks. Stool frequency decreased (2.6 +/- 0.8/d to 1.4 +/- 0.6/d; P < .001). Stool consistency improved from diarrheal to normal form (Bristol Stool Score, 5.3 +/- 0.7 to 3.8 +/- 1.2; P < .001). Pain scores and quality-of-life measures significantly improved. Outcomes were independent of weight loss. CONCLUSIONS: A VLCD provides adequate relief, and improves abdominal pain, stool habits, and quality of life in IBS-D.