Objectives The aim of this study was to evaluate whether the efficiency of the current diagnostic work up following postmenopausal bleeding could be improved by diagnostic strategies that take into account characteristics of the women in addition to the currently recommended transvaginal measurement of endometrial thickness to determine for subsequent histological assessment.Design Multicenter, prospective cohort study.Setting A university hospital and seven teaching hospitals in the Netherlands.Sample Consecutive women not using hormone replacement therapy, presenting with postmenopausal bleeding.Methods Five hundred and forty women underwent transvaginal sonography, and in case of endometrial thickness (double layer) above 4 mm, subsequent endometrial sampling was performed. Presence of carcinoma was ruled out by the absence of abnormalities in histological specimen or by an uneventful follow up of at least 6 months.Main outcome measures Probability of endometrial carcinoma was estimated by multivariable logistic regression models. For each diagnostic strategy, we calculated diagnostic accuracy (area under receiver operating characteristic curve [AUC]), negative predictive value (NPV) and the number of diagnostic procedures. Conclusion Taking into account the characteristics of the women could increase the efficiency of the diagnostic work up for postmenopausal bleeding.