Ophthalmic formulations have classically been administered to eyes through eye drops, which have poor delivery efficiency and require frequent instillation. As a means of overcoming these drawbacks, ocular-drug delivery via therapeutic contact lenses has caused great interest. A simple way to prepare therapeutic contact lenses is to immerse lenses in concentrated drug solution. However, not all ocular drugs can be efficiently loaded into contact lenses by a simple soaking. In particular, our previous study showed that two antibacterial ocular drugs, ofloxacin (OFX) and neomycin (NEO), were poorly loaded to poly(2-hydroxyethyl methacrylate) (pHEMA)-based contact lenses. Herein, we investigated whether alteration of lens composition using several negatively charged comonomers can enhance loading of ocular drugs with poor loadability (OFX and NEO). As comonomers, methacrylic acid (MAA), acrylic acid (AA), and 4-methyl-4-pentenoic acid (MPA) were used, generating p(HEMA-co-MAA), p(HEMA-co-AA), and p(HEMA-co-MPA) hydrogel-based contact lenses, respectively. Contact lenses containing comonomers exhibited an increase in loading of OFX and NEO. In particular, compared with pHEMA contact lenses, contact lenses containing 2.5 mol% AA exhibited enhanced loading of OFX and NEO, 18 and 53 times, respectively. Charge interactions between comonomers and the drug were considered primary factors in the substantial increase in drug loading.