Preterm birth is the greatest threat to the infants in a multiple pregnancy. This chapter focuses on strategies that aim to prevent preterm birth and concentrates on the evidence derived from randomized clinical trials and systematic review of randomized clinical trials. The options to avoid a multiple pregnancy are briefly considered. Interventions that aim to prolong pregnancy, including prophylactic cervical cerclage, prophylactic tocolysis, home uterine activity monitoring and hospitalization for bed rest, are critically appraised, as are interventions that aim to improve the outcome of preterm birth. Interventions that require additional evaluation are highlighted.