Background: Children’s exposures to arsenic (As), lead (Pb), mercury (Hg), and cadmium (Cd) are of particular concern in early-life. Exposures to heavy metals are traditionally measured in whole venous blood, which is costly and invasive. As an alternative we describe a method for quantifying As, Pb, Hg, and Cd in dried blood spot (DBS) samples. Objectives: To validate a method for quantifying levels of As, Pb, Hg, and Cd in finger-stick DBS samples. Background metal contamination in blood collection cards poses a challenge for quantifying heavy metals in DBS samples. Here we report a method to remove background contamination from the filter paper prior to blood collection to improve assay precision. Methods: Matched samples of venous blood and finger-stick DBS samples were collected from 82 children ages 1-21. Whole venous blood samples were also applied to pre-cleaned and untreated blood collection cards. All samples were analyzed for As, Pb, Hg, and Cd using inductively coupled plasma mass spectrometry (ICP-MS). Results: Matched venous blood and finger-stick DBS samples from untreated cards were significantly correlated, but with relatively weak R2 values of 0.083, 0.186, 0.498, and 0.022 for As, Cd, Hg, and Pb, respectively. When blood collection cards were decontaminated prior to blood collection the correlations between venous blood and DBS samples were highly significant, with R2 values of 0.66, 0.99, 0.98, and 0.94 for As, Pb, Hg, and Cd, respectively. Conclusions: Standard blood collection cards contain significant and highly variable background levels of heavy metals. Once blood collection cards are treated to remove residual contamination, DBS sampling can be used as a minimally-invasive alternative to venipuncture to estimate exposures to toxic metals.