In this study conducted in Chicago, IL, intraocular pressure (IOP) level was found to have a subtle, but measurable, annual pattern. Reasonable evidence is presented for a time-of-year variation in IOP. Adequate numbers of subjects must be studied to detect this small variation.Purpose: The aim was to investigate the relationship between IOP and time of year.Methods: During a separate investigation, patients from 2011 to 2018 (dataset A, N = 3041) in an urban, academic facility in Chicago, IL received an examination that included Goldmann applanation tonometry. Regression analyses assessed the relationship between time of year and IOP. Two additional datasets, 1 collected in a similar manner during 1999 and 2002 (dataset B, N = 3261) and another consisting of all first visits during 2012 and 2017 (dataset C, N = 69,858), were used to confirm and further investigate trends.Results: For dataset A, peak mean IOP occurred in December/ January (15.7 ± 3.7/15.7 ± 3.8 mm Hg) and lowest in September (14.5 ± 3.1 mm Hg). The analysis suggested conventional quarterly analysis (January to March, etc.) can conceal time-of-year relationships because of inadequate statistical power and timing of IOP variation. Multiple linear regression analysis, with a November-to-October reordering, detected an annual, downward IOP trend (P < 0.0001). Analysis of dataset B confirmed this trend (P < 0.001). Fourier analysis on datasets A and B combined supported a 12-month IOP cycle for right/left eyes (P = 0.01/P = 0.005) and dataset C provided stronger evidence for an annual periodicity (P < 0.0001). Harmonics analysis of dataset C showed a repeating pattern where IOP trended downward around April, and then back upward around October.Conclusions: This analysis strongly supports a demonstrable annual, cyclical IOP pattern with a trough to peak variation of ≈1 mm Hg, which has a seasonal relationship.