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OBJECTIVE Studies show partial improvements in some core symptoms of Autism Spectrum Disorders (ASD) in time. However, the predictive factors (e.g. pretreatment IQ, comorbid psychiatric disorders, adaptive, and language skills, etc.) for a better the outcome was not studied with machine learning methods. We aimed to examine the predictors of outcome with machine learning methods, which are novel computational methods including statistical estimation, information theories and mathematical learning automatically discovering useful patterns in large amounts of data. METHOD The study the group comprised 433 children (mean age: 72.3 ± 45.9 months) with ASD diagnosis. The ASD symptoms were assessed by the Autism Behavior Checklist, Aberrant Behavior Checklist, Clinical Global Impression scales at baseline (T0) and 12th (T1), 24th (T2), and 36th (T3) months. We tested the performance of for machine learning algorithms (Naive Bayes, Generalized Linear Model, Logistic Regression, Decision Tree) on our data, including the 254 items in the baseline forms. Patients with ≤2 CGI points in ASD symptoms at in 36 months were accepted as the group who has “better outcome” as the prediction class. RESULTS The significant proportion of the cases showed significant improvement in ASD symptoms (39.7% in T1, 60.7% in T2; 77.8% in T3). Our machine learning model in T3 showed that diagnosis group affected the prognosis. In the autism group, older father and mother age; in PDD-NOS group, MR comorbidity, less birth weight and older age at diagnosis have a worse outcome. In Asperger’s Disorder age at diagnosis, age at first evaluation and developmental cornerstones has affected prognosis. CONCLUSION In accordance with other studies we found early age diagnosis, early start rehabilitation, the severity of ASD symptoms at baseline assessment predicted outcome. Also, we found comorbid psychiatric diagnoses are affecting the outcome of ASD symptoms in clinical observation. The machine learning models reveal several others are more significant (e.g. parental age, birth weight, sociodemographic variables, etc.) in terms of prognostic information and also planning treatment of children with ASD.