The MR-Base platform supports systematic causal inference across the human phenome by integrating a curated database of complete genome-wide association study (GWAS) results with an application programming interface, web app, and R packages that automate 2-sample Mendelian randomization (2SMR). The platform includes sensitivity analyses to assess the impact of horizontal pleiotropy and other violations of assumptions. The database currently comprises 11 billion single nucleotide polymorphism-trait associations from 1673 GWAS and is updated regularly. MR-Base ensures more rigorous application of hypothesis-driven analyses and allows millions of potential causal relationships to be efficiently evaluated in phenome-wide association studies. An applied example demonstrates the functionality of MR-Base through an MR study of low-density lipoprotein (LDL) cholesterol and coronary heart disease (CHD), showing strong evidence for violations of assumptions and identifying potential sources of horizontal pleiotropy. The platform also enables hypothesis-free MR-PheWAS analyses, providing insights into potential opportunities for drug repurposing or adverse effects of interventions.The MR-Base platform supports systematic causal inference across the human phenome by integrating a curated database of complete genome-wide association study (GWAS) results with an application programming interface, web app, and R packages that automate 2-sample Mendelian randomization (2SMR). The platform includes sensitivity analyses to assess the impact of horizontal pleiotropy and other violations of assumptions. The database currently comprises 11 billion single nucleotide polymorphism-trait associations from 1673 GWAS and is updated regularly. MR-Base ensures more rigorous application of hypothesis-driven analyses and allows millions of potential causal relationships to be efficiently evaluated in phenome-wide association studies. An applied example demonstrates the functionality of MR-Base through an MR study of low-density lipoprotein (LDL) cholesterol and coronary heart disease (CHD), showing strong evidence for violations of assumptions and identifying potential sources of horizontal pleiotropy. The platform also enables hypothesis-free MR-PheWAS analyses, providing insights into potential opportunities for drug repurposing or adverse effects of interventions.