Objective To test the hypothesis that high numbers of uterine natural killer (uNK) cells in the endometrium of women with recurrent miscarriage (RM) could be reduced with prednisolone. Design A before and after study. Setting A tertiary referral teaching hospital. Patient(s) Eighty-five women with idiopathic RM recruited from all over the UK and 18 women attending for sterilization (controls). Intervention(s) An endometrial sample was taken on day 21 ± 2 of the menstrual cycle. Immunohistochemistry was used to identify uNK (CD56+, CD16−, CD3−). Twenty-nine women with RM and >5% uNK agreed to take 20 mg oral prednisolone daily from day 1 to 21 of their menstrual cycle, when a second biopsy was obtained and analyzed. Main Outcome Measure(s) The percentage of stromal cells that were uNK. The normal range was defined using control samples as <5%. Result(s) Women with RM had significantly more uNK than the controls (P=.008). Prednisolone treatment significantly reduced the number of CD56 cells in the endometrium, from a median of 14% (before) to 9% (after) (P=.0004). Conclusion(s) We have demonstrated that high numbers of uNK in preimplantation endometrium of women with recurrent miscarriage can be reduced with administration of prednisolone.