Post-stroke infections are common complications in acute stroke patients and are associated with an unfavorable functional outcome. However, reports on the effects of prophylactic antibiotics treatment on post-stroke infections are conflicting, especially those on post-stroke pneumonia and outcomes. We searched the PubMed, Embase, and Web of Knowledge databases up through March 11th, 2016. Seven randomized controlled trials including 4261 patients were analyzed among this systematic review and meta-analysis. We found preventive antibiotics treatment at the time of stroke onset did reduce the incidence of infections in adults with acute stroke (OR = 0.57, 95% CI: 0.38–0.85, P = 0.005), including reducing the number of urinary tract infections (OR = 0.34, 95% CI: 0.26–0.46, P < 0.001), but did not significantly decrease the rate of post-stroke pneumonia (OR = 0.91, 95% CI: 0.73–1.13, P = 0.385). Importantly, antibiotics treatment also showed no significant effect on the number of fatalities among stroke patients (OR = 1.07, 95% CI: 0.90–1.26, P = 0.743) and functional outcome scores on the modified Rankin Scale (OR = 1.76, 95% CI: 0.86–3.63, p = 0.124). Our study indicated that preventive antibiotics treatment not reduced the rate of post-stroke pneumonia or mortality, even though decreased the risk of infections, especially urinary tract infections. Thus, preventive antibiotics treatment may not be recommended for acute stroke patients.