Cycloplegic drops are commonly used in ophthalmology practice. Changes in anterior segment parameters may occur after cycloplegia. These changes can be evaluated with corneal topography. This study aimed to compare the effects of 1% cyclopentolate hydrochloride and 1% tropicamide on anterior segment parameters using the Sirius Scheimpflug imaging technique. A cross-sectional study. One hundred twenty eyes of sixty healthy volunteers with spherical equivalent (SE) values of 0 to ±1 diopter (D) were studied. The right eye of each subject had instillation of cyclopentolate hydrochloride 1% (Group 1) and the left eye of each subject had instillation of tropicamide 1% (Group 2). SE, intraocular pressure, and corneal topography measurements were performed before and 40 min after instillation were compared. In Group 1, SE, aqueous depth, anterior chamber depth, iridocorneal angle (ICA), anterior chamber volume (ACV), and pupil size (PS) values were significantly increased (p < 0.001, p = 0.01, p < 0.001, p = 0.03, p < 0.001, and p < 0.001, respectively). In Group 2, SE, ICA, ACV, and PS were significantly increased (p < 0.001 for all). Keratometric values (K1 and K2) and central corneal thickness changed insignificantly in both groups (p > 0.05). The effects of the two administered agents on all parameters were similar (p > 0.05). Cyclopentolate hydrochloride and tropicamide affected SE, ICA, ACV, and PS values significantly. These parameters are important in intraocular lens (IOL) power calculations. PS is also important in refractive surgery and cataract surgery with multifocal IOL implantation. Although there was an insignificant difference between the agents, the effects of tropicamide on the parameters were smaller than those of cyclopentolate.