Incompatibility of leave-on products with an antimicrobial residual can negate the efficacy benefits of chlorhexidine gluconate (CHG) persistence. Two marketed alcohol products containing Carbomer were tested using a pigskin substrate model against Staphylococcus aureus. The CHG residual achieved a 4.22 log(10) reduction (standard deviation [SD] = 0.32) in this study, which was dramatically reduced to a 0.54 (SD = 0.50) and 0.46 (SD = 0.56) after subsequent treatment with incompatible alcohol gel products. A marketed alcohol product containing a nonionic thickener maintained the efficacy of the CHG chemical reservoir (log(10) reduction = 4.26, SD = 0.00). Similar findings were demonstrated when alcohol solutions containing the individual thickening agents were tested as simple formulations. An in vivo test using human forearms and Serratia marcescens similarly demonstrated that the activity of a CHG reservoir (log(10) reduction = 3.73, SD = 0.86) was not reduced by a nonionic thickened product (log(10) reduction = 3.98, SD = 0.72) but was significantly reduced by treatment with alcohol products containing anionic thickeners carbomer (log(10) reduction = -0.32, SD = 0.34) or acrylates/C10-30 alkyl acrylate crosspolymer (log(10) reduction = -0.20, SD = 0.32). The use of anionic thickeners or emulsifiers in leave-on products, including alcohol hand sanitizers, may inactivate the persistent antibacterial activity of CHG.