PurposeTo investigate the prospective association of frailty status with the long-term risk of elderly-onset IBD in a large prospective cohort. MethodsParticipants free of IBD and cancer at enrollment from the UK Biobank cohort were included. Baseline pre-frail and frail status was measured by Fried phenotype including weight loss, exhaustion, low grip strength, low physical activity and slow walking pace, defined as meeting one or two criteria and meeting three or more criteria. Primary outcome was elderly-onset IBD, including elderly-onset ulcerative colitis (UC) and Crohn’s disease (CD). Multivariable Cox regression was conducted to examine the related associations. ResultsOverall, 417,253 participants (aged 56.18 ± 8.09 years) were included. Of whom, 19,243 (4.6 %) and 188,219 (45.1 %) were considered frail and pre-frail, respectively. During a median of 12.4 years follow-up, 1503 elderly-onset IBD cases (1001 UC, 413 CD, and 89 IBD-Unclassified) were identified. Compared with non-frail, individuals with frail (HR=1.40, 95 %CI: 1.13–1.73) and pre-frail (HR=1.15, 1.03–1.28) showed significantly higher risk of elderly-onset IBD after multivariable adjustment (Ptrend<0.001). The positive association was more evident regarding risk of elderly-onset CD (HR=2.16, 1.49–3.13 for frail; HR=1.49,1.20–1.85 for pre-frail; Ptrend<0.001). Sensitivity analyses and subgroup analyses according to age, gender and body mass index (BMI) demonstrated similar results. ConclusionsFrailty and pre-frailty are associated with increased risk of elderly-onset IBD, particularly elderly-onset CD.