Background: Primary postpartum haemorrhage is an obstetrical emergency often causing acute anaemia that may require immediate red blood cell (RBC) transfusion. This anaemia results in symptoms such as fatigue, which may have major impact on the health-related quality of life. RBC transfusion is generally thought to alleviate these undesirable effects although it may cause transfusion reactions. Moreover, the postpartum haemoglobin level seems to influence fatigue only for a short period of time. At present, there are no strict transfusion criteria for this specific indication, resulting in a wide variation in postpartum policy of RBC transfusion in the Netherlands. Methods/Design: The WOMB trial is a multicentre randomised non-inferiority trial. Women with acute anaemia due to postpartum haemorrhage, 12-24 hours after delivery and not initially treated with RBC transfusion, are eligible for randomisation. Patients with severe physical complaints are excluded. Patients are randomised for either RBC transfusion or expectant management. Health related quality of life (HRQoL) will be assessed at inclusion, at three days and one, three and six weeks postpartum with three validated measures (Multi-dimensional Fatigue Inventory, ShortForm-36, EuroQol-5D). Primary outcome of the study is physical fatigue three days postpartum. Secondary outcome measures are general and mental fatigue scores and generic health related quality of life scores, the number of RBC transfusions, length of hospital stay, complications and health-care costs. The primary analysis will be by intention-to-treat. The various longitudinal scores will be evaluated using Repeated Measurements ANOVA. A costs benefit analysis will also be performed. The power calculation is based on the exclusion of a difference in means of 1.3 points or greater in favour of RBC transfusion arm regarding physical fatigue subscale. With missing data not exceeding 20%, 250 patients per arm have to be randomised (one-sided alpha = 0.025, power = 80%). Discussion: This study will provide evidence for a guideline regarding RBC transfusion in the postpartum patient suffering from acute anaemia. Equivalence in fatigue score, remaining HRQoL scores and physical complications between both groups is assumed, in which case an expectant management would be preferred to minimise transfusion reactions and costs. Trial registration: ClinicalTrials.gov NCT00335023, Nederlands Trial Register NTR335 ; Babette W Prick, Eric AP Steegers, AJ Gerard Jansen, Wim CJ Hop, Marie-Louise Essink-Bot, Nina CJ Peters, Carin A Uyl-de Groot, Dimitri NM Papatsonis, Bettina MC Akerboom, Godfried CH Metz, Henk A Bremer, Aren J van Loon, Rob H Stigter, Joris AM van der Post, Marcel van Alphen, Martina Porath, Robbert JP Rijnders, Marc EA Spaanderman, Daniela H Schippers, Kitty WM Bloemenkamp, Kim E Boers, Hubertina CJ Scheepers, Frans JME Roumen, Anneke Kwee, Nico WE Schuitemaker, Ben Willem J Mol, Dick J van Rhenen, and Johannes J Duvekot