Disposable contact lenses worn on a daily-wear basis have been effective in managing patients with giant papillary conjunctivitis. The purpose of this study was to determine which of the available disposable contact lenses, Acuvue (Vistakon, Jacksonville, FL), NewVues (CIBA Vision, Atlanta, GA), and SeeQuence (Bausch & Lomb, Rochester, NY), is superior for managing giant papillary conjunctivitis. Forty-two patients with previously diagnosed giant papillary conjunctivitis were enrolled and monitored at 1-month intervals for 5 months in a prospective, randomized, double-masked study to evaluate the Acuvue, NewVues, and SeeQuence disposable contact lens worn on a daily-year basis for 1 month between lens changes. A detailed analysis of patient preferences with regard to eight symptom variables (itching, discharge, blurred vision, pain, abnormal lens movement, lens awareness, lens handling, and lens comfort) and their overall lens preference was performed monthly. Multivariate regression analysis was performed. When SeeQuence was paired with Acuvue, SeeQuence was preferred for lens movement ( p = 0.0002) and lens handling ( p = 0.0005); Acuvue was preferred for itching ( p = 0.037). When SeeQuence was paired with NewVues, NewVues was preferred for itching ( p = .022), blurred vision ( p = 0.042), pain ( p = 0.029), comfort ( p = 0.030), and overall ( p = 0.024). When Acuvue was paired with NewVues, NewVues was preferred for lens handling ( p = 0.028). Multivariate regression analysis revealed that, of the eight symptom variables tested, lens comfort and lens handling contributed significantly to the overall lens preference in all three paired studies. Lens comfort was at least twice as powerful as lens handling in all cases. No significant changes in papillae were observed. In conclusion, the NewVues outperformed the SeeQuence lens in numerous clinical categories, including overall lens preference. NewVues was significantly preferred over Acuvue only with regard to lens handling. The NewVues was never outperformed. Lens comfort was the most powerful of eight variables contributing to the decisions regarding overall lens preference.