Background: The outcomes of psycho-educational interventions for Autism Spectrum Disorders (ASDs) comorbid with severe to moderate intellectual disability (ID) are insufficiently documented. In this prospective study, we examined a developmental individual, interactive and intensive approach, called the ‘3i method’, which is based on play therapy. Methods: Twenty DSM-IV-TR ASD subjects (mean chronological age 63.8 ± 37.8 months; mean developmental age 19.5 ± 6.6 months) were included and followed the 3i method for 24 months. Developmental and behavioural skills were assessed at baseline and after 24 months using the VABS, PEP-R and Nadel Imitation scale. Autism severity was evaluated using the Child Autism Rating Scale (CARS) and the Autism Diagnostic Interview (ADI-R). Results: After 2 years of the 3i method, our 3 primary outcome variables significantly increased (VABS developmental age of socialization increased by 83%, age of communication by 34%, and Nadel Imitation score by 53%). Almost all VABS and PEP-R domains significantly improved. Additionally, increases in the VABS socialization score were positively correlated with the total number of treatment hours and CARS score; all ADI-R areas significantly decreased; and diagnoses had changed in 47.5% of the subjects (37% for PDD-NOS and even 10.5% for ID without PDD). Conclusion: Children who followed the 3i method for 2 years had significantly improved behavioural and developmental skills and showed a clear decrease in autism severity. These results suggest that the 3i method may be useful for autistic children by improving their daily interactions with their social environment.