The prevalence of multiple pregnancies is increasing over the last few decades. This is due in part due to use of assisted reproductive techniques which are associated with a higher prevalence of multiple gestation compared to spontaneous conceptions. There is considerable evidence to suggest that combined screening for fetal aneuploidies is equally effective for twin pregnancies as it is in singletons. This along with a relatively higher rate of fetal defects requires accurate prenatal diagnosis. There is evidence from large cohort studies, systematic reviews and meta-analysis that the risk of procedure-related loss in singleton pregnancies is not significantly higher than the background rate of miscarriages. The number of studies examining the procedure-related loss in twin pregnancies following invasive procedures is fewer compared to singleton pregnancies. Although the background rate of pregnancy loss is higher in multiple pregnancies compared to singletons, there is evidence from recent systematic reviews and meta-analysis that the procedure-related loss following invasive procedures is not significantly higher compared to the background rate of loss in twin pregnancies. Invasive prenatal procedures in dichorionic and monochorionic multiple pregnancies have unique challenges including technical skill, rates of complications and sampling errors and therefore such procedures should be carried out by experienced operators in Fetal Medicine centres.