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Background There is limited information on differences in plasma lipid levels among the major ethnic groups in Europe. Objective We investigated ethnic differences in plasma lipid levels in a large multiethnic cohort and explored the contribution of obesity and other determinants to ethnic differences in low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglyceride (TG) levels. Methods We compared lipid profiles among 21,617 participants (aged 18 to 70 years) of Moroccan, Ghanaian, South Asian Surinamese, African Surinamese, Turkish and Dutch ethnic origin, living in Amsterdam, the Netherlands. Fasting total cholesterol, HDL-C, and TG were measured while fasting. LDL-C was calculated using the Friedewald formula and corrected for lipid-lowering therapy. Results Mean LDL-C ranged from 2.84 ± 0.22 mmol/L in Moroccans to 3.13 ± 0.06 mmol/L in South Asian Surinamese participants. Mean HDL-C ranged from 1.30 ± 0.15 mmol/L in Turkish to 1.62 ± 0.10 mmol/L in Ghanaian participants. Mean TG ranged from 0.64 ± 1.18 mmol/L in Ghanaian to 1.00 ± 1.18 mmol/L in South Asian Surinamese and 1.00 ± 1.27 mmol/L in Turkish origin participants. The differences in LDL-C, HDL-C, and TG levels remained present after adjustment for age and sex. Differences between ethnic groups were significantly attenuated after adjustment for other determinants, including body mass index, diabetes and use of lipid-lowering drugs but remained significant. Conclusion Large ethnic differences exist in lipid components, especially HDL-C and TG levels with a higher HDL-C and lower TG levels among African (Ghanaian and Surinamese) origin participants and the most unfavorable lipid profiles among individuals of South Asian Surinamese and Turkish origin. Highlights • We investigated ethnic differences in lipid levels in a large multiethnic cohort • Ethnic differences in plasma low-density lipoprotein cholesterol levels are relatively small • Plasma triglyceride and high-density lipoprotein cholesterol levels significantly differ between ethnic groups • We found higher high-density lipoprotein cholesterol and lower triglyceride levels among African origin participants • South Asian Surinamese and Turkish had the most unfavorable lipid profiles [ABSTRACT FROM AUTHOR]