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Statement of problem Tooth extraction therapy serves as a key initial step in many prosthodontic treatment plans. Dentists must make an appropriate decision on the tooth extraction therapy considering multiple determinants and whether a clinical decision support (CDS) model might help. Purpose The purpose of this retrospective records study was to construct a CDS model to predict tooth extraction therapy in clinical situations by using electronic dental records (EDRs). Material and methods The cohort involved 4135 deidentified EDRs of 3559 patients from the database of a prosthodontics department. Knowledge-based algorithms were first proposed to convert raw data from EDRs into structured data for feature extraction. Redundant features were filtered by a recursive feature-elimination method. The tooth extraction problem was then modeled alternatively as a binary or triple classification problem to be solved by 5 machine learning algorithms. Five machine learning algorithms within each model were compared, as well as the efficiency between 2 models. In addition, the proposed CDS was verified by 2 prosthodontists. Results The triple classification model outperformed the binary model with the F1 score of the Extreme Gradient Boost (XGBoost) algorithm as 0.856 and 0.847, respectively. The XGBoost outperformed the other 4 algorithms. The accuracy, precision, and recall of the XGBoost algorithm were 0.962, 0.865, and 0.830 in the binary classification and 0.924, 0.879, and 0.836 in the triple classification, respectively. The performance of the 2 prosthodontists was inferior to the models. Conclusions The CDS model for tooth extraction therapy achieved high performance in terms of decision-making derived from EDRs.