Abstract: Genetic predisposition has been implicated in obesity. Lipoprotein lipase (LPL) gene, the main lipase of chylomicrons and Low Density Lipoproteins (LDL), has a fundamental role in the transport and metabolism of plasma cholesterol. The present study was undertaken to test for the association of the LPL gene Pvu II polymorphism with obesity with or without hypertension and diabetes and dyslipidemia among affected Egyptian cases. This study has included 120 subjects affected with obesity; 57 of them were affected with metabolic syndrome (with diabetes, dyslipidemia and hypertension) while the other 63 cases were not complicated and were termed “simple obesity”. These cases were compared to 83 healthy non-obese controls. Body Mass Index (BMI), Waist Hip Ration (WHR) and serum lipid levels were measured. The LPL gene polymorphic alleles were determined by PCR-RFLP that includes polymerase chain reaction for gene amplification followed by digestion with Pvu II enzyme and analysis according to the size of digested amplified DNA. Obesity cases had a significantly higher frequency of the homozygous mutated LPL Pvu II (+/+) genotype and also of the (+) allele particularly among metabolic syndrome cases compared to controls. Cases with the (+/+) homozygous genotype showed significantly higher frequency of diabetes, lower frequency of positive family history and lower values for waist hip ratio than those with the (+/-) and (-/-) genotypes. These cases have showed also higher levels of total cholesterol and LDL-C, yet not reaching statistical significance. This study showed a significant association between the LPL Pvu II gene polymorphism and obesity among Egyptian cases particularly when complicated with the metabolic syndrome.