The objective of this article was to review clinical outcomes reported with the tissue selective estrogen complex containing bazedoxifene (BZA) and conjugated estrogens (CE) in postmenopausal women. PubMed was searched from inception to June 2011 using the key words bazedoxifene and conjugated estrogens. We reviewed six published articles reporting the clinical efficacy and safety outcomes of three different level I evidence, multicenter, blind, randomized, placebo-controlled studies. BZA/CE reduced hot flush frequency and severity, prevented loss of bone mass, and treated vulvar-vaginal atrophy and its symptoms without endometrial stimulation and provided amenorrhea and breast tenderness rates similar to those with placebo. Overall safety was not different from that observed with placebo, and no unexpected findings were reported. The tissue selective estrogen complex composed of BZA/CE is a new progestin-free therapy that alleviates hot flushes and prevents the loss of bone mass in postmenopausal women with endometrial hyperplasia and amenorrhea rates comparable with those of placebo.