Background:The low fermentable oligosaccharide, disaccharide, monosaccharide, and polyol (FODMAP) diet is effectively manages irritable bowel syndrome (IBS) symptoms. Long-term low-FODMAP studies rarely report quality of life (QoL). We aimed to determine the effect of low-FODMAP diet on long-term QoL, gastrointestinal (GI) and non-GI symptoms in IBS patients. Methods: A prospective observational study of IBS patients referred for low-FODMAP dietary advice was performed. The primary outcome of QoL and secondary outcomes of GI symptoms, anxiety/depression, fatigue, sleep quality, and happiness were obtained at baseline, 6 weeks (T6), and 6 months (T26). Results: 111 patients were recruited. 91.0%, 71.6%, and 50.5% of participants completed baseline, T6, and T26 assessments, respectively. There were significant improvements in QoL from baseline at T6 and T26 (both P < 0.001). Significant reductions were seen in GI symptoms at T6 and T26 (both P < 0.001), fatigue at T6 and T26 (both P < 0.003), and anxiety at T6 and T26 (both P < 0.007), compared with baseline. A significant reduction was seen for depression (P < 0.010) from baseline at T26, and a significant increase was seen for both happiness and vitality (both P < 0.04) from baseline at T26. There was a significant correlation between GI symptom response and change in QoL, anxiety, depression, and fatigue (all P < 0.034). Conclusion: Low-FODMAP diet was associated with improved long-term QoL and GI symptoms, reduced fatigue and anxiety/depression, and increased happiness and vitality. These data support a wider range of benefits for IBS patients consuming a low-FODMAP diet. (Nutr Clin Pract. 2019;34:623-630)