This study evaluated the efficacy of potassium penicillin G in drinking water of weaned pigs to reduce mortality and spread of infection caused by Streptococcus suis. A total of 896 18-day-old weaned pigs were randomly assigned to either treatment with potassium penicillin G in-water (Treated), or no treatment (Control). The outcomes analyzed were total mortality, mortality due to S. suis, and overall counts of S. suis colonies. The risk of mortality due to S. suis and total mortality were significantly increased in the Control group compared with Treated pigs. Bacterial culture of posterior pharyngeal swabs indicated that Control pigs were significantly more likely to have $ 1000 colonies of S. suis per plate than were Treated pigs. This study demonstrates that potassium penicillin G administered in drinking water is effective in reducing mortality associated with S. suis infection and reducing tonsillar carriage of S. suis.