Twins compared with singletons and monozygous (MZ) compared with dizygous (DZ) twins are at increased risk of fetal and infant death, cerebral palsy and many congenital anomalies. The aim of this study is to investigate whether zygosity is a risk factor for the sudden infant death syndrome (SIDS). Birth registration data and draft infant death certificates for all multiple births in England and Wales 1993 to 2003 were provided by the Office for National Statistics. As a partial proxy for zygosity, same-sex was compared with opposite-sex twins for birthweight-specific mortality and mortality attributed to SIDS. Data on singleton infants were obtained by subtraction of multiple births from routinely published population births and infant deaths. SIDS mortality among low birthweight infants was significantly less in twins than singletons. The twin-singleton relative risk was reversed in infants of normal birthweight. Among infants of normal birthweight, neonatal SIDS was significantly more common in same- compared with opposite-sex pairs. Among infants of low birthweight, postneonatal SIDS was significantly more common in same- compared with opposite-sex pairs. The difference in birthweight distribution of same- compared with opposite-sex twins for neonatal SIDS suggests that zygosity is a risk factor for SIDS. As congenital cerebral anomalies are a feature of many monozygous twin conceptions, a detailed macro- and microscopical examination of the brain in twin SIDS may indicate an otherwise unrecognised pathology.