BACKGROUND:The ageing population and prevalence of long-term disorders with multimorbidity are a major health challenge worldwide. The associations between comorbid conditions and mortality risk are well established; however, few prospective community-based studies have reported on prior risk factors for incident hospital admissions with multimorbidity. We aimed to explore the independent associations for a range of demographic, lifestyle and physiological determinants and the likelihood of subsequent hospital incident multimorbidity. METHODS:We examined incident hospital admissions with multimorbidity in 25 014 men and women aged 40-79 in a British prospective population-based study recruited in 1993-1997 and followed up until 2019. The determinants of incident multimorbidity, defined as Charlson Comorbidity Index ≥3, were investigated using multivariable logistic regression models for the 10-year period 1999-2009 and repeated with independent measurements in a second 10-year period 2009-2019. RESULTS:Between 1999 and 2009, 18 179 participants (73% of the population) had a hospital admission. Baseline 5-year and 10-year incident multimorbidities were observed in 6% and 12% of participants, respectively. Age per 10-year increase (OR 2.19, 95% CI 2.06 to 2.33) and male sex (OR 1.32, 95% CI 1.19 to 1.47) predicted incident multimorbidity over 10 years. In the subset free of the most serious diseases at baseline, current smoking (OR 1.86, 95% CI 1.60 to 2.15), body mass index >30 kg/m² (OR 1.48, 95% CI 1.30 to 1.70) and physical inactivity (OR 1.16, 95% CI 1.04 to 1.29) were positively associated and plasma vitamin C (a biomarker of plant food intake) per SD increase (OR 0.86, 95% CI 0.81 to 0.91) inversely associated with incident 10-year multimorbidity after multivariable adjustment for age, sex, social class, education, alcohol consumption, systolic blood pressure and cholesterol. Results were similar when re-examined for a further time period in 2009-2019. CONCLUSION:Age, male sex and potentially modifiable lifestyle behaviours including smoking, body mass index, physical inactivity and low fruit and vegetable intake were associated with increased risk of future incident hospital admissions with multimorbidity.