A dramatic and beneficial effect of ethanesulfonic acid (ESA) on the chiral HPLC separation of basic compounds was found. Using a single chiral column and a starting mobile phase, more than half of a diverse set of amines was baseline separated. Changing alcohol content and alcohol type increased the success rate. Methanesulfonic acid (MSA) proved even more successful. The mechanism of this unexpected finding appears to be a combination of ion-pair salt formation in the mobile phase and increased binding with the chiral stationary phase (CSP) arising from a localized decrease in pH.