We tested the efficacy of nine different intervention strategies to minimize losses associated with experimental coinfection of nursery age pigs with porcine reproductive and respiratory syndrome virus (PRRSV) and Streptococcus suis. The antibimicrobials tested included penicillin, ampicillin, tiamulin, and ceftiofur hydrochloride. Vaccines tested included two commercial modified live PRRSV vaccines, an autogenous killed S. suis vaccine, and an experimental live autogenous S. suis vaccine. We found that the most effective treatment was intramuscular injection of 5 mg/kg ceftiofur hydrochloride on three consecutive days following S. suis inoculation. The live autogenous S. suis vaccine and treatment with ceftiofur hydrochloride every third day for three treatments also significantly reduced mortality.