Purpose.To compare the frequency of mucin balls in subjects wearing conventional and high-Dk silicone hydrogel lenses during 12 months of extended-wear and to determine whether mucin balls are associated with any lens or subject characteristics.Methods.This study used data from a clinical trial where subjects wore either conventional hydrogel (N = 69, 6-night extended-wear) or silicone hydrogel (N = 70, 30-night extended-wear) contact lenses for 12 months. The number of mucin balls and other physiological responses, lens fit and performance, and subjective patient responses to lens wear were rated at each scheduled visit.Results.Subjects in the silicone hydrogel group had significantly greater numbers of mucin balls compared with subjects in the conventional hydrogel group over time (p < 0.001), but there were no significant differences in the percentage of subjects with mucin balls between the two groups. Increasing lens wettability, back surface deposits, and time of lens wear were associated with higher numbers of mucin balls in the conventional hydrogel group (p < 0.05); steeper corneal curvature and increasing lens wettability, back surface deposits, and number of microcysts were associated with higher numbers of mucin balls in the silicone hydrogel group (p < 0.05).Conclusions.This study indicates that a subset of the population is predisposed to develop mucin balls irrespective of the soft contact lens type worn, but lens type influences the degree of mucin ball formation. The relationship between lens wettability, back surface deposits, and steeper corneal curvature with mucin balls supports the hypothesis that the mechanical interaction of a lens with the surface layer of the epithelium and the tear film in association with the blinking forces of the lid is involved in mucin ball formation.