Background Biomarkers of exposures such as infection or environmental chemicals can be measured in small volumes of blood extracted from newborn dried blood spots (DBS) underscoring their potential utility for population-based research. However, few studies have evaluated the feasibility and utility of this resource; particularly the factors associated with parental consent, and the ability to retrieve banked samples with sufficient remaining volume for epidemiologic research. Methods At 8 months postpartum, 5,034 mothers of infants born (2008–2010) in New York (57 counties excluding New York City) were asked to consent for the use of residual DBS for the quantification of cytokines and environmental chemicals. Mothers were part of the Upstate KIDS study, a longitudinal birth cohort designed to evaluate child development through 3 years of age. Information on parental and infant characteristics was obtained from birth certificates and maternal report at 4 months postpartum. Multivariate logistic regression was used to identify factors associated with parental consent and with successful retrieval of DBS. Results Sixty-two percent (n = 3125) of parents consented. Factors significantly associated with consent included non-Hispanic ethnicity (odds ratio 2.04; 95 % CI: 1.43–2.94), parity (1.29; 1.05–1.57), maternal obesity (1.42; 1.11–1.80) and reported alcohol use during pregnancy (1.51; 1.12–2.06). However, these associations corresponded to small absolute differences in proportions (4 to 8 %), suggesting that the two groups remained comparable. Infant characteristics such as preterm delivery did not significantly differ by consent status among singletons and only ventilator use (OR 2.39; 95 % CI: 1.06–5.41) remained borderline significant among twins in adjusted analyses. Among consented infants, 99 % had at least one 3.2 mm punch successfully retrieved for biomarker analyses and 84 % had a full DBS circle available. Conclusion Parental characteristics varied slightly by consent, and the availability of samples for research purposes was high, demonstrating the feasibility of this resource for population based research.