Providers have expressed a strong desire to have additional clinical decision-support tools to help with interpretation of pharmacogenomic results. We developed and tested a novel disease–drug association tool that enables pharmacogenomic-based prescribing to treat common diseases. First, 324 drugs were mapped to 484 distinct diseases (mean number of drugs treating each disease was 4.9; range 1–37).Then the disease–drug association tool was pharmacogenomically annotated, with an average of 1.8 pharmacogenomically annotated drugs associated/disease. Applying this tool to a prospectively enrolled >1,000 patient cohort from a tertiary medical center showed that 90% of the top ∼20 diseases in this population and ≥93% of patients could appropriately be treated with ≥1 medication with actionable pharmacogenomic information. When combined with clinical patient genotypes, this tool permits delivery of patient-specific pharmacogenomically informed disease treatment recommendations to inform the treatment of many medical conditions of the US population, a key initial step towards implementation of precision medicine.