Bisphenol A (BPA) replacement compounds are released to the environment and cause widespread human exposure. However, a lack of thorough safety evaluations on the BPA replacement compounds has raised public concerns. We assessed the endocrine disruption potential of BPA replacement compounds in the market to assist their safety evaluations. A literature search was conducted to ascertain the BPA replacement compounds in use. Available experimental estrogenic activity data of these compounds were extracted from the Estrogenic Activity Database (EADB) to assess their estrogenic potential. An in silico model was developed to predict the estrogenic activity of compounds lacking experimental data. Molecular dynamics (MD) simulations were performed to understand the mechanisms by which the estrogenic compounds bind to and activate the estrogen receptor (ER). Forty-five BPA replacement compounds were identified in the literature. Seven were more estrogenic and five less estrogenic than BPA, while six were nonestrogenic in EADB. A two-tier in silico model was developed based on molecular docking to predict the estrogenic activity of the 27 compounds lacking data. Eleven were predicted as ER binders and 16 as nonbinders. MD simulations revealed hydrophobic contacts and hydrogen bonds as the main interactions between ER and the estrogenic compounds.