Over 13 million people in the United States wear soft contact lenses for refractive correction. Ulcerative keratitis is considered the most serious adverse effect of the use of contact lenses. We performed a case-control study with 86 cases patients, estimating separately for hospital-based (n = 61) and population-based (n = 410) controls the relative risk of ulcerative keratitis among users of extended-wear as compared with daily-wear soft contact lenses. The relative risk of ulcerative keratitis for extended-wear as compared with daily-wear lenses among the population-based controls was 3.90 (95 percent confidence interval, 2.35 to 6.48) and among the hospital-based controls, 4.21 (95 percent confidence interval, 1.95 to 9.08). Thirty-eight percent of those with extended-wear lenses used them only during the day, and 11 percent of those with daily-wear lenses occasionally wore them overnight. When lens wearers were distinguished according to their overnight use of lenses, the users of extended-wear lenses who wore them overnight had a risk 10 to 15 times as great as the users of daily-wear lenses who did not, and the users of daily-wear lenses who sometimes wore them overnight had 9 times the risk of the users of such lenses who did not. For the users of extended-wear lenses, the risk of ulcerative keratitis was incrementally related to the extent of overnight wear. A reduction in risk associated with more frequent attention to lens hygiene was almost significant. We conclude that soft contact lenses worn overnight carry a significantly greater risk for ulcerative keratitis than soft lenses worn only during the day.