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Introduction: Gallstones are increasingly common in children. Genetic analyses of adult cohorts demonstrated that the sterol transporter ABCG8 p.D19H and Gilbert UGT1A1*28 variants enhance the odds of developing gallstones. The genetic background of common lithiasis in children remains unknown. Methods: Overall, 214 children with gallstone disease (1 month–17 years, 107 boys) were inclueded. The control cohorts comprised 214 children (age 6–17 years, 115 boys) and 172 adults (age 40–92 years, 70 men) without gallstones. The ABCG8 p.D19H and UGT1A1*28 polymorphisms as well as ABCB4 (c.504C>T rs1202283, c.711A>T rs2109505) and NPC1L1 variants (p.V1296V rs217434, c.−18C>A rs41279633) were genotyped using TaqMan assays. Serum concentrations of plant sterols and cholesterol precursors were measured by gas chromatography/mass spectrometry. Results: The ABCG8 risk allele was associated with an increased risk of stones (OR = 1.82, p =.03). Children carrying the p.19H allele presented with lower serum concentrations of surrogate markers of intestinal cholesterol absorption and decreased ratios of phytosterols to the cholesterol precursor desmosterol. Carriers of the common NPC1L1 rs217434 allele had an increased gallstone risk compared with stone‐free adults (OR 1.90, p <.01). This variant also affected the ratio of phytosterols to cholesterol precursors (p =.03). Other tested variants were not associated with gallstone risk. Conclusions: The p.D19H ABCG8 and, to a lesser extent, NPC1L1 rs217434 variants increase the risk of early‐onset gallstone formation. These results point to the presence of a common lithogenic pathway in children and adults. [ABSTRACT FROM AUTHOR]