ObjectiveDelivery of therapeutic agents to the cornea is a difficult task in the treatment of parasitic keratitis. In this study, we looked at using different combinations of ultrasound parameters to enhance corneal permeability to polyhexamethylene biguanide (PHMB), a clinically available ophthalmic antiparasitic formulation.MethodsPermeability of PHMB was investigated in vitro using a standard diffusion cell setup. Continuous or 25% duty‐cycle ultrasound was used at frequencies of 400 or 600 kHz, intensities of 0.5 or 0.8 W/cm2, and exposure times ranging from 1 to 5 minutes. Structural changes in the cornea were examined using light microscopy.ResultsUltrasound exposure produced increases in transcorneal delivery in every treatment parameter combination when compared to the sham treatment. The highest increase was 2.36 times for 5 minutes of continuous ultrasound at a frequency of 600 kHz and an intensity of 0.5 W/cm2 with statistical significance (p <.001). Histological analysis showed that ultrasound application only caused structural changes in the corneal epithelium, with most damage being at the surface layers.ConclusionsThis study suggests the possibility of therapeutic ultrasound as a novel drug delivery technique for the treatment of parasitic keratitis. Further studies are needed to examine the thermal effects of these proposed ultrasound applications and the long‐term viability of this treatment.