Objective The ProTWIN Trial (NTR1858) showed that, in women with a multiple pregnancy and a cervical length < 25th percentile (38 mm), prophylactic use of a cervical pessary reduced the risk of adverse perinatal outcome. We investigated whether other maternal or pregnancy characteristics collected at baseline can improve identification of women most likely to benefit from pessary placement. Methods ProTWIN is a multicenter randomized trial in which 808 women with a multiple pregnancy were assigned to pessary or control. Using these data we developed a multivariable logistic model comprising treatment, cervical length, chorionicity, pregnancy history and number of fetuses, and the interaction of these variables with treatment as predictors of adverse perinatal outcome. Results Short cervix, monochorionicity and nulliparity were predictive factors for a benefit from pessary insertion. History of previous preterm birth and triplet pregnancy were predictive factors of possible harm from pessary. The model identified 35% of women as benefiting (95% CI, 32-39%), which is 10% more than using cervical length only (25%) for pessary decisions. The model had acceptable calibration. We estimated that using the model to guide the choice of pessary placement would reduce the risk of adverse perinatal outcome significantly from 13.5% when no pessary is inserted to 8.1% (absolute risk reduction, 5.4% (95% CI, 2.1-8.6%)). Conclusions We developed and internally validated a multivariable treatment selection model, with cervical length, chorionicity, pregnancy history and number of fetuses. If externally validated, it could be used to identify women with a twin pregnancy who would benefit from a pessary, and lead to a reduction in adverse perinatal outcomes in these women. Copyright (C) 2016 ISUOG. Published by John Wiley & Sons Ltd.