This study is a retrospective secondary analysis of data from the C-STICH randomized controlled trial, which included women at high risk of preterm birth who received vaginal cervical cerclage. Of the 2048 women in C-STICH, 1943 (95%) had cerclage and progesterone data; 834 (43%) received progesterone and 1109 (57%) did not. The primary outcome was pregnancy loss (abortion and perinatal mortality). Among women with available data, pregnancy loss occurred in 49 (5.9%) of 832 with progesterone and in 91 (8.3%) of 1103 without progesterone. The adjusted hazard ratio was 0.70 (95% CI [0.50, 0.99]; hazard difference −0.04 [−0.04, −0.001]), adjusted for indication, obstetric history, operative technique, and maternal age. The combination of cerclage with progesterone was associated with a reduced risk of pregnancy loss in this high-risk group. The study was conducted in 75 maternity units in the UK between 2015–2021.