Intraocular pressure (IOP) has been shown to change with body position. Several studies have shown that the lateral decubitus position (LDP) is associated with a significant increase in IOP in the dependent eye. However, whether anesthetic agents alter IOP in the LDP remains unclear. This study investigated the effect of sevoflurane and propofol anesthesia on IOP in the LDP. A total of 28 patients undergoing surgery in the LDP were included. Patients were randomly allocated to sevoflurane or propofol groups. IOP in both eyes was recorded and compared between groups at five time points: after anesthesia induction, after endotracheal intubation, at 5 min and 1 h after a positional change to the LDP, and 5 min after returning to the supine position. In the sevoflurane group, IOP was significantly increased in both dependent and non-dependent eyes 1 h after changing to the LDP. In the propofol group, IOP decreased in both dependent and non-dependent eyes after tracheal intubation, but did not increase after changing to the LDP. The number of patients in whom IOP increased to ≥28 mmHg was greater in the sevoflurane group than in the propofol group. Propofol may be better than sevoflurane for the maintenance of anesthesia in the LDP. Monitoring of IOP in the LDP might help avoid ophthalmic complications.