BACKGROUND: The combined effects of some modifiable lifestyle factors on incident inflammatory bowel disease (IBD) are uncertain. AIMS: To evaluate the combined association between healthy lifestyle behaviours and IBD incidence. METHODS: This population-based prospective cohort study used data from the UK Biobank. We included 105,715 participants aged 40-70 who had no IBD diagnosis at baseline in the analyses. The five healthy lifestyle behaviours that we studied were never smoking, optimal sleep, high level of vigorous physical activity, high dietary quality, and moderate alcohol intake. The outcome was the overall incidence of IBD and individual incidences of Crohn's disease (CD) and ulcerative colitis (UC). We derived hazard ratios (HR) and 95% confidence intervals (CI) for associations. RESULTS: The multivariable adjusted HRs (95% CI) associated with having 1, 2 and 3-5 healthy lifestyle behaviours for IBD incidence compared with those with none of these behaviours were 0.75 (0.59-0.97), 0.72 (0.56-0.92), and 0.50 (0.37-0.68), respectively (p for trend <
0.001). We observed similar findings for CD and UC. Only never smoking exhibited significant independent inverse associations with the overall incidence of IBD (HR 0.70, 95% CI 0.58-0.83, p <
0.001) and the incidence of UC (HR 0.58, 95% CI 0.48-0.72, p <
0.001). CONCLUSIONS: Healthy lifestyle behaviours are significantly associated with lower IBD incidence in middle-aged and elderly individuals, suggesting the potential of lifestyle modifications as a primary prevention strategy for IBD.