The PRISM trial is the largest ever randomised trial in miscarriage prevention; it recruited more than 4000 women from 48 hospitals in the UK. It evaluated the effects of progesterone hormone in women with early pregnancy bleeding. Overall, there was a 3% increase in live birth rate with progesterone, compared with placebo, but the finding was associated with some statistical uncertainty (RR 1.03, 95% CI 1.00 to 1.07, p = 0.08). However, a clear benefit was found for women with the dual risk factors of early pregnancy bleeding and a history of (any number of) previous miscarriages (RR = 1.09, 95% CI 1.03 to 1.15, p = 0.003). The larger the number of previous miscarriages, the greater the live birth rate, with progesterone treatment. For women who had 1 or 2 previous miscarriages, and have current pregnancy bleeding, progesterone was associated with a 4% increase in live birth. For women with 3 or more previous miscarriages, and have current pregnancy bleeding, progesterone was associated with a 15% increase in live birth. There were no evidence of any safety concern from progesterone use. Our clinical recommendation is that for women with early pregnancy bleeding and a history of any number of previous miscarriages, progesterone treatment should be considered. Our recommended regimen is vaginal Utrogestan 400mg twice daily from the time of presentation with bleeding to 16 weeks of gestation. This trial was funded by the NIHR-HTA programme, and supported by the Tommy’s National Centre for Miscarriage Research. The trial was led from the Institute of Metabolism and Systems Research at the University of Birmingham, facilitated by the Birmingham Clinical Trials Unit.