BACKGROUND: In this study, we evaluated the effects of various medications on the patency of vascular access (VA) for hemodialysis. METHODS: We analyzed data from the Longitudinal Health Insurance Database of Taiwan. We adopted a case-control study design within a cohort of patients who had received regular hemodialysis between 2002 and 2012; 34,354 patients with first VA failure were identified, and the duration from VA creation date to the first VA failure date was calculated. We then classified these patients into two groups, namely arteriovenous fistula (AVF, n = 25,933) and arteriovenous graft (AVG, n = 8,421). Each group was further divided into two subgroups, namely short-term (<1 year) and long-term (≥1 year) patency. RESULTS: The risk factors for early VA failure were age ≥65 years, diabetes mellitus, hyperlipidemia, cerebral vascular disease, congestive heart failure, peripheral artery disease, and sepsis. Male sex, hypertension, cancer, and peptic ulcer were associated with early AVF failure. Antiplatelet therapy increased the AVF and AVG patency times with adjusted odds ratios of 0.748 (95% confidence interval [CI]: 0.703-0.796, p < 0.0001) and 0.810 (95% CI: 0.728-0.901, p = 0.0001), respectively. A significant decrease in the VA failure risk was observed with an increase in the cumulative defined daily dose of antiplatelet agents. CONCLUSION: This nationwide study demonstrated that some risk factors were associated with early VA failure and that the use of antiplatelet agents prevented the loss of VA patency in a dose-response manner. Thus, antiplatelet drugs should be routinely administered to high-risk patients receiving dialysis.