<b>Purpose</b> To investigate the time course of pupil centration following application of common topical ocular drugs. <b>Method</b> Single drops of each of 2.5% phenylephrine hydrochloride, 1% tropicamide, and 2% pilocarpine hydrochloride were applied on different days to the right eyes of 12 participants. Anterior eye images were captured, at 5 minute intervals for an hour, using an infrared-sensitive camera. The images were analysed to determine pupil diameter and pupil center, the latter with respect to the limbal center. As a control, natural pupil size and pupil center were determined under different illuminances. <b>Results</b> Pupil centers of natural pupils shifted temporally as pupils dilated. At common pupil sizes, drug-induced pupil centers were different from natural pupil centers. Phenylephrine produced a center shift in the nasal and inferior directions that peaked after a mean 30 minutes, while dilation was continuing up to 60 minutes. Tropicamide produced transient center shifts in the nasal and inferior directions that peaked at about 10 minutes before reducing towards baseline values, while dilation reached a peak at about 25 minutes. Pilocarpine produced a small sustained superior shift that, like constriction, reached a peak after about 25 minutes. <b>Conclusion</b> Application of topical ophthalmic drugs cause shifts in pupil center that do not match those produced by natural changes in pupil size, and that in the cases of phenylephrine and tropicamide follow a different time course than the pupil size changes.