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Objective: To evaluate endometrial BCL6 expression as a prognostic biomarker for IVF outcome in women with unexplained infertility (UI) before ET., Design: Prospective cohort study., Setting: University-associated infertility clinic., Patient(s): Women with UI for >1 year., Intervention(s): We studied women with UI who underwent testing for endometrial BCL6, in an LH-timed midluteal phase biopsy and completed an IVF cycle and ET., Main Outcome Measure(s): Clinical pregnancy rate (PR) and live birth rate per transfer was compared for women positive or negative for BCL6 expression. An abnormal BCL6 result was defined by an histologic score (>1.4)., Result(s): Women with normal and abnormal BCL6 and those who conceived or not had similar characteristics. Women with low levels of BCL6 expression had a significantly higher clinical PR (11/17; 64.7%; 95% confidence interval [CI] 41.3-82.6) compared with women with abnormal (high) BCL6 expression (9/52; 17.3%; 95% CI 9.3-30.8). These results yield a relative risk of 0.267 (95% CI 0.13-0.53; P=.0004) for those with normal BCL6 expression, an absolute benefit of 47.4% (95% CI 22.5-72.0). Live birth rate was also significantly higher in women with low BCL6 expression (10/17; 58.8%; 95% CI 36.0-78.4) compared with women with abnormal BCL6 expression (6/52; 11.5%; 95% CI 5.4-23.0). The relative risk was 0.19 (95% CI 0.08-0.45; P=.0002), yielding an absolute benefit of 47.3% (95% CI 21.8-67.8)., Conclusion(s): Aberrant BCL6 expression (histologic score, >1.4) was strongly associated with poor reproductive outcomes in IVF cycles in women with UI., (Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.)