Background: Hyperbaric Oxygen Therapy (HBOT) is a recommended treatment for all hypoxic-ischemic pathologies. It has been demonstrated that perfusion abnormalities are present in some areas of cerebral grey matter in autistic children and there is a lack of connectivity in areas of the white matter. The cause of these anomalies is still unknown. The areas involved (temporal lobes, frontal lobes, and other areas such as the thalamus, limbic circuits, corpus callosum, and cerebellum) are connected to the symptoms and behavior of these patients. The PET and SPECT scans demonstrate how low pressure HBOT facilitates the oxygenation of hypoxic cerebral areas in autistic children. The clinical trials recorded in the literature are still insufficient for clarifying many elements. Goals: To demonstrate that HBOT leads to significant improvements in specific abilities and behavioral symptoms tied to the functioning of the affected brain areas, and to show the safety of the HBOT treatments. Materials and Methods: Thirty children between five and nine years old, randomized, with autism spectrum disorder (ASD) underwent HBOT at 1.5 ATA and 100% oxygen for a total of 40 sessions. The following eight psychometric scales were used for the analysis: VMI (Visual-Motor Integration), PPVT (receptive-auditory language), BRIEF (executive function), SRS (social responsiveness scale), VABS (adaptive behavior), ABC (aberrant behavior), PSI (parental distress index), A.T.E.C. (analysis of treatment outcomes). Multiple statistical tests were used, based on the requirements of each specific analysis. Results: Improvement was found in the following areas/abilities: receptive-auditory vocabulary (p=0.016), visual-motor integration (p=0.045), visual perception (p= 0.004), motor coordination (p=0.049), “SHIFT” scale (p=0.013), subscale I/irritability (p=0.001), subscale II/lethargy (p=0.015), subscale III/stereotypic behavior (p=0.040), subscale IV/hyperactivity (p=0.000), subscale V/inappropriate speech (p=0.008) on the ABC test, communication scale (p=0.000), global scale of adaptive behavior (p=0.001), and in the outcomes of the treatment (p=0.029). A decrease was found on the social awareness subscale (p= 0.21). The analysis of the ABC subscale revealed that there were also significant improvements during the course of the treatment. Conclusions: A significant probability of obtaining positive clinical results using HBOT in subjects affected by ASD was demonstrated. No side effects were observed in any of the children who were treated.