Purpose To compare the success rate of extraocular muscle surgery and botulinum toxin injection for treatment in patients with acute acquired comitant esotropia (AACE). Patients and Methods This is a retrospective cohort study in which we treated 34 patients of AACE with botulinum toxin compared with 80 patients who had been treated with surgery. The data included angle of deviation in prism diopter (PD) at baseline and one, three, and six months after treatment. The main outcome was the success rate in each treatment group. Results In the surgery group, mean esodeviation angles at baseline and one, three, and six months after treatment were 50.8 ± 18.3 PD, 4.9 ± 8.3 PD, 4.6 ± 9.5 PD, and 5.5 ± 10.3 PD, whereas those in the botulinum toxin group were 51.2 ± 14.3 PD, 13.9 ± 17.4 PD, 22.0 ± 19.3, and 31.3 ± 23.8 PD, respectively. There was a statistically significant difference in the deviation angles between the two groups ( p < 0.001). The success rate in the surgery group at one, three, and six months was 81%, 84%, and 79%, whereas that in the botulinum toxin group was 50%, 27%, and 27%. Conclusion Botulinum toxin injection was not as effective as conventional extraocular muscle surgery in AACE patients. However, the treatment is safe, fast-acting, and improves both cosmetic appearance and quality of life. This may be considered as a chance for patients not preferring surgery.