Prosthetic joint infections (PJIs) are among the most devastating complications after joint replacement. There is limited evidence regarding the efficacy of different antiseptic solutions in reducing planktonic microorganism burden. The purpose of this study was to test the efficacy of different antiseptic solutions against clinically relevant planktonic microorganisms. We designed an experiment examining the efficacy of several antiseptic solutions against clinically relevant planktonic microorganisms in vitro. Regarding planktonic microorganisms, povidone-iodine had 99.9% or greater reduction for all microorganisms tested except for methicillin-resistant Staphylococcus aureus, which was reduced by 60.44%. Irrisept (Irrimax Corp) had 99.9% or greater reduction for all microorganisms except Staphylococcus epidermidis (98.31%) and Enterococcus faecalis (48.61%). Bactisure (Zimmer Surgical Inc) had 99.9% or greater reduction for all microorganisms tested. Various measures exist for PJI prevention, one of which is intraoperative irrigation. We tested irrigants against clinically relevant planktonic microorganisms in vitro and found significant differences in efficacy among them. Further clinical outcome data are necessary to determine whether these solutions can impact PJI in vivo. [Orthopedics. 2022;45(2):122-127.].