Background: Asians and Pacific Islanders in the Hemochromatosis and Iron Overload Screening (HEIRS) Study had the highest prevalence of elevated serum ferritin (SF) and transferrin saturation (TS) levels, but to our knowledge, the reasons for this have not been investigated. Methods: Using multiple linear regression, we compared TS and SF distributions for 42 720 Asian, Pacific Islander, and white HEIRS Study participants recruited through 5 field centers in North America who did not have HFE C282Y or H63D alleles. Results: Compared with their white counterparts, Asian men had a 69-ng/mL (155-pmol/L) higher adjusted mean SF level and a 3% higher TS level (P<.001); Asian women had 23-ng/mL (52-pmol/L) higher adjusted mean SF level and a 3% higher TS level (P<.001). The mean TS level of Asian women was higher than that of Pacific Islander women, and the mean SF level of Pacific Islander men was significantly higher than that of white men. These differences remained significant after adjusting for self-reported history of diabetes or liver disease. Additional information for selected participants suggested that these differences are largely unrelated to mean corpuscular volume less than 80 fL,body mass index, or self-reported alcohol intake. Available liver biopsy and phlebotomy data indicated that iron overload is probably uncommon in Asian participants. Conclusion: Higher TS and SF levels in persons of Asian or Pacific Island heritage may need to be interpreted differently than for whites, although the biological basis and clinical significance of higher levels among Asians and Pacific Islanders are unclear.