<p>Urinary tract infections (UTIs) are a major complication in patients with acute-to-subacute stroke. Asymptomatic bacteriuria is prevalent in this population, and the role of prophylactic antibiotics remains unclear. This study evaluated whether prophylactic antibiotics reduces the incidence of symptomatic UTI in patients with acute-to-subacute stroke with asymptomatic bacteriuria. This retrospective cohort study analyzed 111 patients with acute-to-subacute stroke and asymptomatic bacteriuria at a Taiwanese medical center. Participants were stratified into intervention (<i>n</i> = 38, receiving oral prophylactic antibiotics) and control (<i>n</i> = 73, no antibiotics) groups. The study compared the incidence of urinary tract infections between two groups. A subgroup analysis of subacute patients with stroke was performed to confirm the antibiotics’ protective effect. UTI incidence in the intervention and control groups were 2.7% and 32.73%, respectively (<i>p</i> = 0.003). Multivariate logistic regression revealed a 93% reduced risk of symptomatic UTI in the intervention versus the control group (<i>p</i> = 0.025). Subgroup analysis demonstrated the persistent protective effect of oral prophylactic antibiotics (<i>p</i> = 0.036). Prophylactic antibiotic treatment effectively reduced symptomatic UTI incidence among patients with acute-to-subacute stroke with asymptomatic bacteriuria. Future multicenter randomized controlled trials are warranted to standardize treatment protocols and evaluate long-term outcomes in this vulnerable population.</p>