It is widely accepted that maternal drug-exposed infants demonstrate excessive early weight loss, but this has not previously been quantified. Among 354 term, substitute methadone-exposed infants, median maximal weight losses were 10.2% and 8.5% for breast- and formula-fed infants, respectively (p=0.003). Weight loss was less in small for gestational age compared to appropriately grown infants (p<0.001). There was no association between maximal weight loss and plasma sodium concentration (p=0.807). Relative to non-drug exposed infants, weight loss was more marked in formula-fed infants, 48% of whom demonstrated weight loss in excess of the 95th centile (compared to 23% of exclusively breastfed infants; p<0.001). Median weight loss nadir was on day 5, excepting those infants exclusively breastfed (day 4). These data suggest that excessive neonatal weight loss among breastfed infants of drug-misusing mothers does not necessarily reflect poorly established lactation and may help to guide management of breast feeding in this population.