Background. Many ambulatory children with spina bifida (SB) decline in their walking despite stable or even improved motor function. Objective. The authors evaluated the effects of a home-based treadmill training program on both ambulatory function and aerobic fitness. Methods. This randomized clinical trial of 34 ambulatory children with SB allocated 18 to supervised treadmill training for 12 weeks at home and 14 to usual care. Patients in home training exercised twice a week at an intensity of 66% of HR_peak (peak heart rate) and gradually progressed from 70% to 140% of their individual walking speed. Main outcome measures were obtained at baseline, after intervention, and 3 months postintervention. Ambulation was measured using the 6-minute walk test (6MWT), during which gross energy consumption (ECS_gross) and energy cost were calculated. Maximal exercise capacity was measured using an incremental treadmill test. Both VO_2peak and speed_peak were recorded as outcome parameters. Results. After training, significant changes were seen between the groups for 6MWT ( P = .002; d = 1.08), speed_peak ( P = .001; d = 1.14), VO_2peak ( P = .034; d = 0.78), and ECS_gross ( P = .004; d = 1.01). Long-term effects were recorded for 6MWT ( P = .003; η = 0.34), speed_peak ( P = .003; η = 0.35), and ECS_gross ( P = .014; η = 0.29) but not for VO_2peak. Conclusion. A home-based, progressive treadmill training program for ambulatory children with SB has a large long-term effect on ambulation, with a moderate short-term effect on VO_2peak.