We studied the use of a complete hemostatic profile for evaluating postmenopausal (PMP) women with histories of thrombosis or phlebitis who were presenting for hormone replacement therapy (HRT). Eighteen PMP women with histories of thrombotic or phlebitic symptoms who presented to our Menopausal Unit for HRT underwent complete hemostatic profiles, and decisions regarding HRT use were made based on the results and concurrent risk-factor analysis. Nine of 18 women had a hemostatic abnormality: one protein C, six protein S, one activated protein C resistance, and one anticardiolipin (ACA) antibody. None of the patients with protein C or S deficiencies subsequently received HRT. The patient with a positive ACA has used HRT with coumadin, without incident. Five of the nine patients with normal profiles have been treated with HRT without any short-term complications. A complete hemostatic evaluation thus aids in diagnosing underlying hypercoagulable states and may be useful for directing medical decisions regarding HRT for PMP women with histories of thrombosis or phlebitis.