Background: A genome-wide association study identified rs1466113 (G>C) in the somatostatin receptor 2 (SSTR2) gene as one of the polymorphisms most significantly associated with body mass index (BMI). As replication is required, we examined the association between this polymorphism and anthropometric variables and food intake in a Mediterranean population. Methods: We studied 945 high cardiovascular-risk subjects (340 men and 605 women) aged 67 ± 6 years, participating in the PREDIMED-Valencia Study. Demographic, clinical, biochemical, dietary, genetic and anthropometric data were obtained. Results: We found recessive effects for the association between this polymorphism and anthropometric variables. Homozygous subjects for the C allele had significantly lower BMI than G-allele carriers (29.9 ± 4.5 in CC vs. 31.0 ± 4.9 in GG + GC; p = 0.035). Likewise, odds ratio for obesity was lower in CC subjects in comparison with G-allele carriers, even after adjustment for potential confounders (odds ratio: 0.60, 95% confidence interval: 0.38–0.94; p = 0.028). We also found significant differences in food (meats, dairy products and legumes) and nutrient (protein) intakes between CC- and G-allele carriers. Conclusion: The rs1466113 polymorphism in the SSTR2 gene is associated with anthropometric variables in the Mediterranean population replicating previous results in the Framingham study. We also observed differences in food intake between genotypes.