The aim of this study was to identify clinical and demographic factors associated with misalignment after first surgery performed on children affected by infantile esotropia to evaluate the reoperation rate. A retrospective study was carried out, analyzing data from 525 children who underwent bilateral medial recti recession, bilateral lateral recti resection, and inferior oblique recession and anteroposition by the same surgeon (AM). Postoperative evaluation included assessment of motor alignment at approximately 3 months, 6 months, 1 year, and 5 years. Statistical analysis was performed with a logistical regression model in which the dependent variable was the presence/absence of reoperation. We found that late surgery (after 3 years of age) and a family history of strabismus are associated with a higher risk of reoperation, while some clinical factors, including some classically associated with worst motor outcome as preoperative angle, dissociated vertical deviation, and amblyopia, did not influence the incidence of reoperation in infantile esotropia. Male patients and patients with hyperopia in preoperative examinations have a significantly decreased reoperation rate.