Down syndrome (DS) is one of the most common genetic disorders and often associated with feeding problems and tube feeding. Although feeding tubes have a life sustaining function, tube dependency can occur including adverse effects such as frequent vomiting, poor appetite and oral aversion. Although various tube weaning programs exist, their effectiveness in children with DS has been studied only to a limited extent. This study investigated outcomes and growth parameters in tube-dependent children (TDC) with DS who participated in a program based on the “Graz Model of tube weaning”. The current international prospective cohort study included 33 TDC with DS treated between April 2013 and July 2023 (median age: 1.67 years; IQR: 1.00–4.35). Growth data (weight-for-age z scores [WAZ], height-for-age z scores [HAZ], and BMI z scores [zBMI]) were evaluated before and after weaning. The study assessed treatment duration and predictors of weaning success. Overall success rate was 91.67% with an average treatment duration of 79 days. Duration of weaning for younger children (<3 years) tended to be shorter. Post treatment, significant reductions in WAZ (p = .001) and zBMI (p < .001) occurred. HAZ remained constant. The only significant predictor of treatment duration was the degree of change in zBMI and HAZ (p = .001). This study demonstrated that the “Graz model of tube weaning” is effective in the great majority of TDC with DS. Results showed moderate weight loss but that this did not affect overall growth. Future studies should evaluate long-term nutritional and developmental outcomes post-weaning.