Objective: To assess the effectiveness of an interdisciplinary ambulatory rehabilitation programme for persons with spina bifida in an Australian community cohort. Methods: Fifty-four participants randomized to a treatment group (n = 27) for a high-intensity rehabilitation programme (with cognitive behavioural therapy) or a control group (n = 27) comprising usual care. Outcome measures include: Disability: Urogenital Distress Inventory (UDI6), Incontinence Impact Questionnaire-7 (IIQ7), American Urological Association Symptom Index (AUA), Wexner-Faecal Incontinence Score (WFIS), Neurological Disability Scale (NDS); Participation: Depression, Anxiety Stress Scale (DASS), McGill Quality of Life (MQOL), Brief COPE Scale, Generalized Self-efficacy Scale (GSE). Assessments were made at baseline and 3-months post-intervention. Results: Adjusted for baseline disease and demographic covariates, the intervention group improved significantly at 3-month follow-up for primary and secondary outcomes, with moderate to large effect sizes (r): urinary/bowel dysfunction (AUA, UDI6, IIQ7, WFIS) (p <0.001 for all, r = 0.4-0.7); and cognitive function: NDS cognitive and mood (p <0.01, r = 0.6 for both); DASS depression , anxiety and stress (p <0.001 for all, r = 0.5-0.7); MQOL total (p = 0.013, r = 0.5), psychological symptoms (p <0.001, r = 0.8); active coping (p = 0.035) and self-efficacy scores (GSE p <0.001). No difference between groups was noted in other subscales. Conclusion: Targeted rehabilitation can improve clinical outcomes in persons with spina bifida. Further research is needed for longer-term outcomes related to ageing and participation restriction.