This chapter discusses the systematic analysis process on the estimations of the prevalence levels for diseases and their sequelae in population in the GBD study. Section 5.1 provides an overview of the International Classification of Diseases and Injuries (ICD) and the current status of the data to provide context for the GBD study. Section 5.2 compares similarities and differences between the GBD classification of diseases and injuries and ICD-10; then, it reviews the sources of data, data quality, and adjustment strategy of data in the GBD study. The main data adjustments prior to entering the model include age–sex splitting, bridging between different standardized data, and adjustments to hospital data. Section 5.3 reviews the strategies and processes used by the GBD study to estimate the prevalence levels of more than 300 diseases and their sequelae for populations in global, regional, and country levels using the DisMod-MR model and other models, respectively. Sections 5.4 and 5.5 describe the GBD group’s strategies and processes for estimating the prevalence levels of different diseases, using cardiovascular and cerebrovascular diseases and cancers as examples, respectively, for explaining the characteristics of the estimation strategies for specific diseases. Section 5.6 summarizes the characteristics and significance of the GBD study’s systematic analysis for estimating prevalence level of diseases and injury. The central tenets of the GBD study is comparing with different outcome measures, which challenges the principle of Cochrane meta-analysis.