Hormone replacement therapy (HRT) relieves menopausal symptoms and improves quality of life. Also, estrogen-based regimens are needed for feminizing gender-affirming hormone therapy (GAHT). However, estrogen therapies may evoke thrombotic complications, and thus, modified estrogens that preserve desirable estrogenic actions, while minimizing thrombogenic liability are needed. We synthesized two aminoestrogen enantiomers, R-β-Mefenetame and S-β-Mefenetame. Their structures were confirmed by elemental analysis, mass spectrometry, 1 H nuclear magnetic resonance, infrared spectroscopy, and single-crystal X-ray diffraction. Antiaggregant activity was evaluated in a murine model measuring whole-blood clotting time and whole-blood platelet impedance aggregometry. R-β-Mefenetame increased whole-blood clotting time further than S-β-Mefenetame. Both enantiomers decreased collagen-induced platelet aggregation by roughly 30% and did not modify ADP-induced aggregation under the conditions tested. Enantioselective activity differences prompted molecular docking analyses on the G protein-coupled estrogen receptor (GPER1), where higher selectivity of R-β-Mefenetame than S-β-Mefenetame was observed, offering a plausible mechanism for differences in hemostatic activity. Data also include silico ADME and toxicology profiling, identifying high lipophilicity, high plasma protein binding, predicted CYP2D6/CYP3A4 inhibition, and a potential hERG liability that should be addressed in future optimization. R-β-Mefenetame is a promising aminoestrogen that should be further evaluated for antiaggregant activity and hemostatic effects in more comprehensive thrombosis models.