Symptoms of bacterial and fungal keratitis are typically treated through the frequent application of antibiotic and antifungal eye drops. The high frequency of half hourly or hourly eye drop administration required to treat these indications is tedious and could reduce compliance. Here, we combine in vitro experiments with a mathematical model to develop therapeutic soft contact lenses to cure keratitis by extended release of suitable drugs. We specifically focus on increasing the release duration of levofloxacin and chlorhexidine from 1-DAY ACUVUE® TrueEye™ and ACUVUE OASYS® contact lenses by incorporating vitamin E diffusion barriers. Results show that 20% of vitamin E loading in the contact lens increases the release duration of levofloxacin to 100 h and 50 h from 1-DAY ACUVUE® TrueEye™ and ACUVUE OASYS®, respectively, which is a 3- and 6-fold increase, respectively, for the 2 lenses. For chlorhexidine, the increase is 2.5 and 10 fold, for the TrueEye™ and OASYS®, respectively, to 130 h and 170 h. The mass of drug loaded in the lenses can be controlled to achieve a daily release comparable to the commonly prescribed eye drop therapy. The vitamin E–loaded lenses retain all critical properties for in vivo use.