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Previous studies have shown marked variability in the outcome of autistic children and have reported different prognostic factors related to this issue.The current study was carried out to (a) examine and compare the outcome of autism in a sample of Egyptian and Saudi patients from a comprehensive point of view over a period of 2 years and (b) identify factors and prognostic variables related to outcome.The study included 48 children with autism. They were recruited from the Institute of Psychiatry, Ain Shams University, Cairo, Egypt, and the Al-Amal complex for Mental Health, Dammam, Kingdom of Saudi Arabia. The diagnosis was made according to Diagnostic and Statistical Manual of Mental Disorders, 4th ed. The sample included 20 Egyptian and 28 Saudi patients. They were assessed at baseline and at follow-up after 2 years. Assessment included clinical assessment, the Clinical Global Impression – Improvement Scale, the Childhood Autism Rating Scale, the Gilliam Autism Rating Scale, the Vineland Adaptive Behavioral Scale, and the Stanford Binet intelligence quotient test.Good outcome among the entire sample was significantly correlated with higher age of noticing abnormality, higher intelligence quotient, mild severity of autism, fairly high scores on the Vineland scale, and low stereotypy scores. There was a tendency toward a better outcome in the Egyptian group compared with the Saudi group. However, this tendency was not statistically significant. In the Egyptian group, there was a significant decrease in Gilliam subscales scores, indicating improvement in autism level, with no significant improvement in Vineland subscales. In the Saudi group, there was an improvement in the Gilliam stereotype subscale and worsening in the Vineland total and subscales. Good outcome among the entire sample was also significantly associated with having atypical autism, absence of seizures, or regression; normal milestones of development, high parental concern, having normal electroencephalography, taking no drugs or being stable on one drug therapy, early behavioral intervention, receiving phoniatric therapy, and improvement of more than two core deficits in response to drug therapy.The outcome of autism appears to be related to certain influential factors such as the severity of autism, familial and clinical factors, perinatal and developmental factors as well as method of dealing and intervening with autism. Specifically, initial severity of autism, parental concern, and early intervention with behavioral approaches appear to be the strongest predictors of the outcome of autism.