Preterm birth is the major contributor to perinatal mortality and serious neonatal morbidity, and approximately 30% of all patients admitted to a neonatal intensive care unit in the Netherlands are born from a multiple pregnancy. In asymptomatic women with a multiple pregnancy and short cervix, prophylactic use of a cervical pessary might reduce preterm birth. The aim of this study is to assess the possible treatment effects of pessary use in pregnancy duration and for poor perinatal outcome. This cohort study was performed between December 2012 and September 2014 in 44 hospitals in the Netherlands. Cervical length was measured between 16 and 22 weeks of gestation. When cervical length was below 38 mm, women were offered a cervical pessary. The pessaries were removed at 36 weeks of gestation or in case of premature rupture of the membranes, active vaginal bleeding, other signs of preterm labor, or severe patient discomfort. The course of pregnancy, including perinatal outcome in these women, was compared with the outcome of women from the placebo group of the AMPHIA trial (ISRCTN40512715) (historical cohort). Propensity score matching with replacement was used to create comparable baseline characteristics between both populations. The study included 63 women in the pessary group and 56 women as control subjects. Propensity score matching generated 57 women in the intervention group matched to 57 women (31 unique) in the control group. Gestational age at delivery was comparable between both groups (hazard ratio, 0.96; 95% confidence interval [CI], 0.46–1.46), as well as their delivery rates before 28, 32, and 37 weeks (RR, 0.68 [95% CI, 0.21–2.18]; RR, 0.54 [95% CI, 0.21–1.41]; and RR, 1.22 [95% CI, 0.47–3.15]), respectively. There was no difference in composite perinatal outcome (RR, 1.36 [95% CI, 0.53–3.51]) and perinatal mortality (RR, 0.89 [95% CI, 0.24–3.38]) either. Results of this cohort study with propensity score analysis could not confirm the positive effect of pessary therapy in the prevention of preterm birth in asymptomatic multiple pregnancies with a short cervix in this propensity score analysis. With ongoing studies on this subject, the definite answer whether pessaries are effective in the prevention of preterm birth will come. If effective, evaluation of implementation, similar to this study, is still necessary.