AbstractMultimorbidity (the presence of two or more long-term conditions [LTCs]) was suggested to exacerbate the neuronal injuries. The impact of multimorbidity on dementia has not been fully elucidated. We aimed to investigate the association between multimorbidity and dementia risk. We used the prospective data from 245,483 UK Biobank participants during a 9-year follow-up. Multimorbidity status was evaluated based on the LTC counts and multimorbidity patterns. Cox regression models adjusted for potential confounders were used to examine the associations of multimorbidity status with all-cause dementia (ACD), Alzheimer’s disease (AD) and vascular dementia (VD). Participants with multimorbidity at baseline had higher risks of ACD and VD, and the risks were elevated with the increase of LTC counts (ACD: hazard ratios [HR] = 1.15, 95% confidence intervals [CI] = 1.01–1.31 with 2 LTCs; HR = 1.18, CI = 1.01–1.39 with 3 LTCs; HR = 1.65, CI = 1.44–1.88 with ≥4 LTCs; VD: HR = 1. 66, CI = 1.24–2.21 with 2 LTCs; HR = 2.10, CI = 1.53–2.88 with 3 LTCs; HR = 3.17, CI = 2.43–4.13 with ≥4 LTCs). Participants with ≥4 LTCs also had a higher risk of AD (HR = 1.34, CI = 1.08–1.66]. Participants with the cardio-cerebrovascular/respiratory/metabolic/musculoskeletal/depressive multimorbidity were 1.46, 1.28, and 2.50 times more likely to develop ACD (HR = 1.46, 95% CI = 1.28–1.67), AD (HR = 1.28, CI = 1.04–1.58), and VD (HR = 2.50, CI = 1.90–3.27), respectively. Those with tumor/genitourinary/digestive disorders had a 11% higher hazard of ACD (HR = 1.11, CI = 1.00–1.24) and a 73% elevated risk of VD (HR = 1.73, CI = 1.37–2.18). The prevention of LTC accumulation and the identification of specific multimorbidity patterns might be beneficial to the prevention of dementia and its subtypes, AD as well as VD.