There is increasing interest in the use of gluten- and casein-free diets for children with autism spectrum disorders (ASDs). We report results from a two-stage, 24-month, randomised, controlled trial incorporating an adaptive 'catch-up' design and interim analysis. Stage 1 of the trial saw 72 Danish children (aged 4 years to 10 years 11 months) assigned to diet (A) or non-diet (B) groups by stratified randomisation. Autism Diagnostic Observation Schedule (ADOS) and the Gilliam Autism Rating Scale (GARS) were used to assess core autism behaviours, Vineland Adaptive Behaviour Scales (VABS) to ascertain developmental level, and Attention-Deficit Hyperactivity Disorder - IV scale (ADHD-IV) to determine inattention and hyperactivity. Participants were tested at baseline, 8, and 12 months. Based on per protocol repeated measures analysis, data for 26 diet children and 29 controls were available at 12 months. At this point, there was a significant improvement to mean diet group scores (time*treatment interaction) on sub-domains of ADOS, GARS and ADHD-IV measures. Surpassing of predefined statistical thresholds as evidence of improvement in group A at 12 months sanctioned the re-assignment of group B participants to active dietary treatment. Stage 2 data for 18 group A and 17 group B participants were available at 24 months. Multiple scenario analysis based on inter- and intra-group comparisons showed some evidence of sustained clinical group improvements although possibly indicative of a plateau effect for intervention. Our results suggest that dietary intervention may positively affect developmental outcome for some children diagnosed with ASD. In the absence of a placebo condition to the current investigation, we are, however, unable to disqualify potential effects derived from intervention outside of dietary changes. Further studies are required to ascertain potential best- and non-responders to intervention. The study was registered with ClincialTrials.gov, number NCT00614198.