PURPOSE: To determine whether central corneal thickness (CCT) correlates with measured intraocular pressure (IOP) response to topical ocular hypotensive medication in the Ocular Hypertension Treatment Study (OHTS). DESIGN: Prospective randomized clinical trial. METHODS: Intraocular pressure measurements were performed by Goldmann applanation tonometry. Central corneal thickness was measured by ultrasonic pachymetry. The following indicators of IOP response to topical ocular hypotensive medication were examined: (1) IOP after an initial four- to six-week one-eyed therapeutic trial of a nonselective beta-blocker (N = 549) or a prostaglandin analog (N = 201); (2) the mean IOP response during 12 to 60 months of follow-up among medication participants (N = 689); (3) the percentage of follow-up visits at which both eyes met the treatment goal; (4). the total number of different medications prescribed to reach treatment goal; and (5) the total number of different medications prescribed multiplied by the number of months each medication was prescribed. RESULTS: Central corneal thickness was inversely related to the IOP response after the initial one-eyed therapeutic trial and during 12 to 60 months of follow-up (P < .05). Mean CCT was not correlated with the number of different medications prescribed during follow-up, the total medication-months, or the percentage of visits at which IOP target was met. CONCLUSIONS: Individuals with thicker corneas had smaller measured IOP responses to ocular hypotensive medication than those with normal or thin corneas. We believe that CCT measurements may be useful in patient management and in interpreting clinical trials of ocular hypotensive medication.