Background: Myelomeningocele is a common birth defect that is often accompanied by clubfoot deformity. Treatment of clubfoot associated with myelomeningocele traditionally has consisted of extensive soft-tissue release operations, which are associated with many complications. The purpose of the present study was to evaluate the early results of the Ponseti method for the treatment of clubfoot associated with myelomeningocele. Methods: Sixteen consecutive patients with myelomeningocele (twenty-eight clubfeet) and twenty consecutive patients with idiopathic clubfeet (thirty-five clubfeet) were followed prospectively while being managed with the Ponseti method. The average duration of follow-up was thirty-four months for the myelomeningocele group and thirty-seven months for the idiopathic group. Clubfoot severity was graded at the time of presentation with use of the Diméglio system. The initial correction that was achieved, casting and/or bracing difficulties, recurrences, and subsequent treatments were evaluated and compared between the two cohorts by means of appropriate statistical analysis. Results: Eleven (39%) of the twenty-eight clubfeet in the myelomeningocele group were graded as Diméglio grade IV, compared with only four (11%) of the thirty-five clubfeet in the idiopathic group (p = 0.014). Initial correction was achieved in thirty-five clubfeet (100%) in the idiopathic group and in twenty-seven clubfeet (96.4%) in the myelomeningocele group (p = 0.16). Relapse of deformity was detected in 68% of the feet in the myelomeningocele group, compared with 26% of the feet in the idiopathic group (p = 0.001). Relapses were treated successfully without the need for extensive soft-tissue release surgery for all but four of the clubfeet in the myelomeningocele group and for all but one of the clubfeet in the idiopathic group (p = 0.16). Conclusions: Our data support the use of the Ponseti method for the initial treatment of clubfoot deformity associated with myelomeningocele, although attention to detail is crucial in order to avoid complications. Longer follow-up will be necessary to assess the risk of late recurrence and the potential need for more extensive clubfoot corrective surgery in this patient population. Level of Evidence: Prognostic Level II. See Instructions to Authors for a complete description of levels of evidence.