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Background The prevalence of multiple long-term conditions (MLTCs) is increasing and having a bigger impact on people’s lives and care systems. There is little evidence on early-life interventions to prevent this problem. Therefore, we explored the association between five early-life domains and the outcome of having MLTCs with role-limitation, and modelled early-life prevention scenarios using evidence of effectiveness from real-life interventions.Methods We analysed data from 6201 participants in the 1970 British Cohort Study, which follows individuals born in 1970. The outcome was self-reported two or more MLTCs with role-limitation (i.e. impacting everyday life functioning) due to a physical or mental health condition at age 46. The exposures were adversity scores within early-life domains including: prenatal to birth, developmental attributes, education, socioeconomic factors, and family environment. Multivariable logistic regression was used, adjusting for sex, ethnicity, and adult factors including exercise, education, income, smoking, partnership status, financial difficulty, alcohol consumption, and media usage. Adjusted population attribution fractions (PAFs) modelled the reduction in outcome risk if cohort members reduced their adversity scores. Effect estimates on early-life exposures from evaluations of real-life interventions including Family Hubs, the Family Nurse Partnership, and the teenage pregnancy prevention framework (that targets sex and relationship education and access to contraception and support), calculated the absolute reduction in the outcome risk had cohort members been exposed to the combined effect of these interventions.Results 11.8% of cohort members reported MLTCs with role limitations. Adjusted PAFs demonstrated that reducing adversity scores from 3+ to 1 (19.5% 95%CI 6.1%-29.7%), from 3+ to 0 (25.8% 95%CI 13.0%-37.9%), from 2 to 0 (16.6% 95%CI 0.8%-27.6%) in the developmental attributes domain, and from 3+ to 2 (20.0% 95%CI 2.4%-34.4%), from 3+ to 0 (24.0% 95%CI 8.0%-37.2%), from 1 to 0 (13.0% 95%CI 0.1%-24.3%) in the prenatal to birth domain, significantly lowered the outcome risk. For the developmental attributes domain, modelling the combined exposure to interventions and applying corresponding PAFs led to 0.5% absolute reduction in outcome risk amongst those with a domain adversity score of 3+. For the prenatal to birth domain, modelling the combined exposure to interventions and applying corresponding PAFs led to a 11.5% and 2.5% absolute reduction in outcome risk amongst those with a domain adversity score of 3+ and 1, respectively.Conclusion Real life interventions relevant to the pregnancy or postnatal period and/or developmental adversity in childhood may have a long-term impact on the risk of MLTCs in midlife.