To investigate the causes of graft failure and risk factors associated with total graft opacity after primary penetrating keratoplasty (PK) in children with Peters anomaly (PA). In this retrospective study, patients with PA (younger than 5 years) who received primary PK in Beijing Tongren Hospital were reviewed. The follow-up period was a minimum of 6 months. A modified PA classification system was used, and all failed grafts were categorized into partial and total opacity groups. Patient demographics, PA classification, operation details, degree of graft opacity, and causes of graft failure were recorded. Of the 165 eyes, 54 eyes (32.7%) demonstrated graft failure along with various degrees of graft opacity. Approximately half of the grafts applied failed within 6 months postoperatively. The partial and total opacity groups did not demonstrate any significant differences regarding diagnosis distribution. Irreversible immune rejection accounted for 61.1% of all graft failures; furthermore, it had a significantly higher proportion in the partial opacity group than in the total opacity group (71.0% and 47.8%, respectively; P = 0.058). The degree of graft opacity was significantly associated with patient age at surgery (P = 0.002), preoperative corneal vascularization (P = 0.009), and iris defects (P = 0.001). However, administration of intensive topical corticosteroids could reduce the risk of total opacity in the rejected grafts. Irreversible immune rejection is the most common cause of graft failure after primary PK in pediatric patients with PA. The degree of graft opacity is closely related to patient age at surgery, preoperative corneal vascularization, and iris defects.