Purpose: To evaluate the effects of different contact lens (CL) replacement schedules and different CL materials on the ocular surface and tear function. Methods: Daily disposable hydrogel CLs were given to group 1 (n = 22), daily disposable silicone hydrogel CLs were given to group 2 (n = 25), and reusable silicone hydrogel CLs were given to group 3 (n = 24). Tear function tests and inflammatory cytokine [ interleukin (IL)-6, IL-8, IL-17A, and matrix metalloproteinase (MMP)-9] levels were evaluated before and at 1 and 3 months after CL usage. Impression cytology was evaluated before and at 3 months after CL usage. Results: At the first and third months of CL usage, a statistically significant difference was determined between the groups in the levels of IL-6, IL-8, and IL-17A in tears, with the lowest levels in group 1 and the highest levels in group 3 (all P, 0.05). At the third month of CL usage, the levels of these cytokines (in picograms/ milliliter) were 6.06 6 0.83, 78.18 6 12.42, 61.69 6 13.95, and 37.71 6 5.95 in group 1 and 8.04 6 0.89, 107.34 6 14.40, 68.63 6 13.72, and 46.26 6 6.50 in group 3, respectively. A statistically significant decrease was determined over time in the Schirmer test in group 1, in only the tear breakup time in group 2, and in the tear breakup time and Schirmer test in group 3 (all P, 0.05). A statistically significant increase was determined over time in the levels of IL-6, IL-8, IL-17A, and MMP-9 in all groups. In the third month, a significant progression was observed in the Nelson grade (P, 0.05) in all groups. Conclusions: The wear of daily disposable CLs can be considered to cause less damage to the ocular surface and less increase in proinflammatory cytokine levels.