To determine the optimal duration of monocular occlusion in patients with intermittent exotropia. This prospective cohort study enrolled 40 patients with intermittent exotropia at Ramathibodi Hospital between May 2023 and September 2023. Angles of deviation at distance (6 m) and near fixation (0.33 m) were measured before and after monocular occlusion for 30, 60, and 90 minutes. All measurements were performed by a single ophthalmologist. The mean angle of deviation was calculated at each time point. The mean age at presentation was 12.5 years (range, 5-33 years). The mean angles of deviation before monocular occlusion were 27.8 ± 15.1 prism diopters (PD) at distance and 26 ± 13.7 PD at near fixation. At distance, mean angles of deviation after monocular occlusion were 32.2 ± 14.6, 32.9 ± 15.0, and 32.6 ± 14.7 PD at 30, 60, and 90 minutes, respectively. At near fixation, mean angles of deviation after monocular occlusion were 37.4 ± 15.0, 39.8 ±14.3, and 39.5 ± 14.6 PD at 30, 60, and 90 minutes, respectively. All angles significantly differed from the pre-occlusion deviation (all P < 0.01). For deviation at distance, there was no statistically significant difference between 60 and 30 minutes of monocular occlusion (P = 0.48). For deviation at near fixation, there was a significant difference between 60 and 30 minutes of monocular occlusion (P = 0.048), but the difference of 2.5 PD was not clinically significant. There were no statistically significant differences between 90 and 60 minutes of monocular occlusion at distance or near fixation (both P = 0.82). Monocular occlusion is necessary to eliminate the fusion effect in patients with intermittent exotropia; 30 minutes of monocular occlusion is sufficient to achieve the maximum angle of deviation.