Objective: To examine the relationship between intraocular pressure (IOP) readings taken by the Tone-Pen tonometer (Mentor O and O, Norwell, MA) and central corneal thickness (CCT). Design: Prospective cross-sectional population study. Participants: There were 651 eyes of 332 healthy subjects. Main Outcome Measures: A questionnaire was given to each subject requesting information on gender, age, race, and other factors that can influence IOP. The IOP then was measured using the Tone-Pen followed by measurements of CCT using an ultrasonic pachymeter. Results: The IOP was found to increase by 2.9 mmHg/100 μm CCT in males and 1.2 mmHg/100 μm in females. For males, CCT was found to be statistically significant in predicting IOP (P < 0.001 in the right and left eyes) and diabetes was of borderline significance (P = 0.012 in the right eye, P = 0.089 in the left eye). For females, CCT was of borderline significance (P = 0.064 in the right eye, P = 0.019 in the left eye). In females, a family history of glaucoma (P = 0.021 in the right eye, P = 0.022 in the left eye) and hypertension (P = 0.010 in the right eye, P = <0.001 in the left eye) were also significant in the prediction of IOP. Race was found to be a significant predictor of CCT (P < 0.001 in both right and left eyes) for both males and females. Conclusion: Clinicians should be aware that, as with the Goldmann applanation tonometer, the Tone-Pen has a systematic error in lOP readings caused by its dependence on CCT. Tone-Pen IOP readings are positively correlated to CCT in males and, to a lesser extent, in females as well. The CCT measurements should be considered to ensure proper interpretation of lOP measurements in the diagnosis and management of disorders in which the CCT or IOP readings are outside normal limits.