BACKGROUND Polycystic kidney disease (PKD) is a genetic disorder characterized by the growth of numerous cysts within the kidneys. Disease progress of some patients often occurs at the early stage. Thus, managing and controlling disease progress is important to slow the kidney function decline especially for the patient with other disorders. CASE SUMMARY One 80-year-old male autosomal dominant polycystic kidney disease (ADPKD) patient with chronic kidney disease and other clinical disorders was treated with tolvaptan and edoxaban. Estimated glomerular filtration rate, creatinine and uric acid were monitored during the treatment. In addition, the whole exome sequencing was performed to screen ADPKD genetic variants. The kidney function decline was prevented after using tolvaptan and edoxaban treatment and in the meantime, a venous thromboembolism was removed and leg and pedal edema were alleviated. One mutation c.10102G > A /p.D3368N in the PKD1 gene was identified. CONCLUSION Tolvaptan combined with edoxaban administration could delay kidney function decline and eliminate the edema caused by the thromboembolism.