. The APOA4 Thr 347 3 Ser 347 polymorphism is not a major risk factor of obesity. Obes Res. 2005;13:2132-2138. Objective: The goal of this study was to assess the association between the APOA4 Thr 347 3 Ser 347 polymorphism and BMI and obesity. Research Methods and Procedures: Men and women (n ϭ 3320), randomly recruited in three independent population surveys from the north, east, and south of France, were genotyped for the APOA4 Thr 347 3 Ser 347 polymorphism. Results: There were 1327 overweight (825 men, 502 women) and 611 obese (313 men, 298 women) subjects. The prevalences of subjects carrying at least one Ser 347 allele (*/Ser 347 ) were 36.5%, 33.8%, and 34.3% in controls, overweight, and obese subjects, respectively (not significant), and those of the Ser 347 /Ser 347 genotype were 4.5%, 3.0%, and 2.2%, respectively (not significant). In both men and women, mean BMI and body weight were not significantly different among APOA4 genotypes. There was no evidence of heterogeneity among centers, smoking status, alcohol intake, physical activity, and educational level categories. In men, mean waist girth was lower in Ser 347 /Ser 347 (92.2 Ϯ 9.4 cm) than in Thr 347 carriers (95.9 Ϯ 10.9 cm; p ϭ 0.01), and plasma triglycerides levels were lower in Ser 347 (1.41 Ϯ 1.04 mM) than in Thr 347 /Thr 347 carriers (1.55 Ϯ 1.23 mM; p ϭ 0.01). Discussion: These results suggest that the APOA4 347Ser allele is not a major risk factor for obesity or overweight.