Objectives The management strategies of postmenopausal bleeding (PMB) vary between different centres. This study was conducted to (1) evaluate the performance of a “One Stop PMB Clinic” that uses trans-vaginal ultrasound scanning (TVS) ± Pipelle ® endometrial biopsy (EB) as the first line investigation, and (2) identify the risk factors for endometrial cancer to help setting criteria to prioritize clinic slots. Study design A retrospective data review of 326 women seen in the period from 1 August 2005 until 31 August 2009 at Ipswich Hospital, UK. Results The median primary referral interval was 30 days. The prevalence of endometrial cancer and atypical hyperplasia was 5.5% ( n = 18) and 1.8% ( n = 6), respectively. One case with endometrial thickness (ET) of <5 mm and negative Pipelle ® EB was found to have cancer on a curettage specimen taken for persistent bleeding. Statistical analysis revealed an association between endometrial cancer and increased ET ( p < 0.0001), increased age ( p = 0.004) and multiple episodes of bleeding ( p = 0.04). There was no evidence of an association with parity ( p = 0.64) or severity of bleeding ( p = 0.46). There was no case of endometrial cancer in HRT users. Conclusion TVS ± Pipelle ® EB may be a safe first line investigation in managing PMB. Accepting that all investigations have a false negative rate, women with persistent bleeding should be re-investigated. Given the ever-increasing workload, the priority for urgent appointments may be given to the older women, non-users of HRT and those with multiple episodes rather than heavy bleeding.