Background A common mitochondrial DNA variant, that is maternally inherited, the 16189 variant, is associated with type 2 diabetes and thinness at birth. In order to elucidate the association of the variant with thinness, we studied the 16189 variant in a well characterised Australian cohort (n=161) who were followed up from birth to age 20 years. Methods PCR analysis and mtDNA haplotyping was carried out on DNA from 161 offspring from consecutive, normal singleton pregnancies were followed from birth to ages 20. Results The 16189 mt DNA variant was present in 14 of the 161 20 year olds (8.7%). Both the mothers with the 16189 variant and their 20 year old offspring were thinner than those without. Median (IQR) BMI was 21.9 (20.4 to 22.9) in mothers with the variant compared with 23.5 (21.4 to 26.6) in those without (p=0.013), and 22.2 (21.1 to 23.8) in 20 year olds with the variant compared with 22.7 (20.8 to 25.6) in those without (p=0.019). The 16189 variant was also associated with a high placental weight and high placental to birth weight ratio (p=0.051 and p=0.0024 respectively). Insulin sensitivity was normal in 20 year olds with the 16189 variant. This contrasts with 20 year olds who did not have the variant but who had been thin or small at birth, who had normal BMI and normal placental to birth weight ratio, but were insulin resistant. Conclusion This study suggests that 16189 mt DNA variant is associated with maternally inherited thinness in young adults. This may be mediated by effects on mtDNA replication and thence placental function. Further research is required to confirm these hypotheses.