Objective: The report compares the differences in the impact of VBP generic drugs and original drugs on the main clinical outcome indicators in the treatment of major diseases, and promotes the rational use of VBP drugs in the clinical practice. Methods: The main focus is on the effectiveness and safety of the second and third batches of VBP drugs in clinical diagnosis and treatment. The paper investigates a total of 29 representative medical institutions in 16 provinces and municipalities in China, covering six major categories of cardiovascular, anti-tumor, neuropsychiatric, anti-infection, metabolic and endocrinic, and digestive systems. We extract baseline information and research indicators related to drug treatment and clinical outcomes from medical record data for efficacy, safety, and economic evaluation. Statistical analysis is conducted with inter-group baseline correction and analysis method of outcome indicators. Result: There is no statistically significant difference in the effectiveness and safety between the selected generic drugs in the national centralized procurement and the original drugs, providing evidence-based basis for rational clinical medication. Conclusion: This study provides an important reference for clinical doctors in decision-making of drug use, promotes the clinical rational use of selected drugs in centralized procurement, provides evidence-based data for the implementation of national centralized procurement policies, and also provides a model and method for the implementation and effectiveness evaluation of national centralized procurement policies.