Objective: To develop a random forest model (RFM) to predict implantation potential of a transferred embryo and compare it with a multivariate logistic regression model (MvLRM), based on data from a large cohort including in vitro fertilization (IVF) patients treated with the use of single-embryo transfer (SET) of blastocyst-stage embryos. Design: Retrospective study of a 2-year single-center cohort of women undergoing IVF or intracytoplasmatic sperm injection (ICSI). Setting: Academic hospital. Patient(s): Data from 1,052 women who underwent fresh SET in IVF or ICSI cycles were included. Intervention(s): None. Main Outcome Measure(s): The performance of both RFM and MvLRM to predict pregnancy was quantified in terms of the area under the receiver operating characteristic (ROC) curve (AUC), classification accuracy, specificity, and sensitivity. Result(s): ROC analysis resulted in an AUC of 0.74 ± 0.03 for the proposed RFM and 0.66 ± 0.05 for the MvLRM for the prediction of ongoing pregnancies of ≥11 weeks. This RFM approach and the MvLRM yielded, respectively, sensitivities of 0.84 ± 0.07 and 0.66 ± 0.08 and specificities of 0.48 ± 0.07 and 0.58 ± 0.08. Conclusion(s): The performance to predict ongoing implantation will significantly improve with the use of an RFM approach compared with MvLRM.