This study compared the clinical behavior of disposable and frequent replacement Acuvue and 1-Day contact lenses. Each type of lens was worn on one eye according to the schedule recommended by the manufacturer, and on the other eye for a longer period of time, up to 30 days in length. Both type of lenses were prescribed on a daily-wear basis. The amount of protein collected from the lenses was measured using two spectrophotometric protein assays. Visual acuity and comfort, along with several other clinical signs, were classified according to Cornea and Contact Lens Research Unit (CCLRU) scales, and possible associations between each of these signs and the amount of protein extracted from the lenses was tested. A comparison between the lens worn on the compliant eye with the lens worn on the noncompliant eye allowed us to measure the impact of overwear on ocular health and subjective clinical findings. After four months of study, the overwear of Acuvue and 1-Day lenses significantly increased the amount of protein bound on the contact lenses, as well as the severity of upper conjunctival papillae, upper lid conjunctival hyperemia, and limbal congestion. Even if reduced values for visual acuity and noninvasive break-up time (NIBUT) were identified, these variations were not found to be statistically significant. The clinical implications of this study would allow a practitioner to identify, according to the variations in several clinical signs, a patient who overwears contact lenses, so that action may be taken to reduce possible deleterious effects on ocular health.