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Background: Multimorbidity is characterized by the co-occurrence of 2 or more chronic diseases and has been a focus of the health care sector and health policy makers due to its severe adverse effects., Objective: This paper aims to use the latest 2 decades of national health data in Brazil to analyze the effects of demographic factors and predict the impact of various risk factors on multimorbidity., Methods: Data analysis methods include descriptive analysis, logistic regression, and nomogram prediction. The study makes use of a set of national cross-sectional data with a sample size of 877,032. The study used data from 1998, 2003, and 2008 from the Brazilian National Household Sample Survey, and from 2013 and 2019 from the Brazilian National Health Survey. We developed a logistic regression model to assess the influence of risk factors on multimorbidity and predict the influence of the key risk factors in the future, based on the prevalence of multimorbidity in Brazil., Results: Overall, females were 1.7 times more likely to experience multimorbidity than males (odds ratio [OR] 1.72, 95% CI 1.69-1.74). The prevalence of multimorbidity among unemployed individuals was 1.5 times that of employed individuals (OR 1.51, 95% CI 1.49-1.53). Multimorbidity prevalence increased significantly with age. People over 60 years of age were about 20 times more likely to have multiple chronic diseases than those between 18 and 29 years of age (OR 19.6, 95% CI 19.15-20.07). The prevalence of multimorbidity in illiterate individuals was 1.2 times that in literate ones (OR 1.26, 95% CI 1.24-1.28). The subjective well-being of seniors without multimorbidity was 15 times that among people with multimorbidity (OR 15.29, 95% CI 14.97-15.63). Adults with multimorbidity were more than 1.5 times more likely to be hospitalized than those without (OR 1.53, 95% CI 1.50-1.56) and 1.9 times more likely need medical care (OR 1.94, 95% CI 1.91-1.97). These patterns were similar in all 5 cohort studies and remained stable for over 21 years. A nomogram model was used to predict multimorbidity prevalence under the influence of various risk factors. The prediction results were consistent with the effects of logistic regression; older age and poorer participant well-being had the strongest correlation with multimorbidity., Conclusions: Our study shows that multimorbidity prevalence varied little in the past 2 decades but varies widely across social groups. Identifying populations with higher rates of multimorbidity prevalence may improve policy making around multimorbidity prevention and management. The Brazilian government can create public health policies targeting these groups, and provide more medical treatment and health services to support and protect the multimorbidity population., (©Xi-liang Li, Hang Huang, Ying Lu, Randall S Stafford, Simone Maria Lima, Caroline Mota, Xin Shi. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org), 30.05.2023.)