Bisphenol S (BPS) has been widely substituted for bisphenol A (BPA) on thermal papers, but little is known about its skin absorption.We compared the percutaneous absorption and biotransformation of BPS and BPA in vitro and in a controlled human trial.Absorption and biotransformation of BPS and BPA were monitored across reconstructed human epidermis at two environmentally relevant doses over 25 h. In the human trial, five male participants handled thermal receipts containing BPS and washed their hands after 2 h. Urine (0-48 h) and serum (0-7.5h) were analyzed for target bisphenols, and one participant repeated the experiment with extended monitoring. BPS data were compared with published data for isotope-labeled BPA ([Formula: see text]) in the same participants.At doses of 1.5 and [Formula: see text] applied to reconstructed human epidermis, the permeability coefficient of BPS (0.009 and [Formula: see text], respectively) was significantly lower than for BPA (0.036 and [Formula: see text], respectively), and metabolism of both bisphenols was negligible. In participants handling thermal receipts, the quantities of BPS and [Formula: see text] on hands was significantly correlated with maximum urinary event flux ([Formula: see text]), but the slope was lower for BPS than BPA ([Formula: see text] and 1.1, respectively). As a proportion of total urinary bisphenol, free BPS [[Formula: see text]: [Formula: see text]] was higher than for free BPA ([Formula: see text]). Postexposure maximum urinary BPS concentrations (0.93 to [Formula: see text]; [Formula: see text]) were in the 93-98th percentile range of BPS in background Canadians ([Formula: see text]; [Formula: see text]).Both the in vitro and human studies suggested lower percutaneous absorption of BPS compared with BPA, but a lower biotransformation efficiency of BPS should also be considered in its evaluation as a BPA substitute. https://doi.org/10.1289/EHP5044.