Background: Type 2 diabetes mellitus (T2DM) is one of the world's most common diseases with a high prevalence and incidence. Objective: To investigate the association of APOA1 polymorphism (-75 G/A) with dyslipidemia and susceptibility to CAD among Egyptian patients with T2DM. Patients and Methods: A total number of 72 subjects with T2DM and 72 age and sex matched healthy controls were enrolled for the study. T2DM patients were subdivided to T2DM without CAD (n=36) and T2DM with CAD (n=36). Genotyping of the APOA1 was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) combined with gel electrophoresis, and then confirmed by direct sequencing. Results: Our findings revealed that GA and AA genotypes and A allele of APOA1 G-75A were significantly higher in controls than T2DM without CAD cases. Also, GA and AA genotypes and A allele of APOA1 G- 75A were significantly higher in controls than T2DM with CAD cases. The risk of CAD were significantly lower among patients carrying GA and AA genotypes than those carrying GG genotype (OR (95%CI): 0.16 (0.06-0.48), P<0.001; OR (95%CI): 0.08 (0.01-0.78), P<0.01, respectively). Our findings revealed significantly higher values of HDL in AA genotype of APOA1 G-75A compared to GA and GG. On the other hand, there were significantly lower values of TC and TG in AA genotype of APOA1 G-75A compared to GA and GG. Conclusions: The individuals with the APOA1 -75 GA and AA genotypes and A allele were likely to have a lower risk of T2DM and CAD as a result of its effect on HDL-C serum levels.