Polymorphism of the haptoglobin (Hp) gene, characterized by alleles Hp1 and Hp2, gives rise to structurally and functionally distinct Hp protein phenotypes: Hp1-1, Hp2-1, and Hp2-2. The corresponding proteins have structural and functional differences that have influence on a particular disease. For example, Hp genotype is an independent risk factor for diabetic complications. In urban Ghana, type two diabetes mellitus (T2DM) affects at least 6% of adults. The aim of this study was to assess the association between Hp genotype polymorphism in T2DM patients in Accra. The study was a case control one. A total of 100 participants, 50 T2DM patients attending the Diabetes Clinic (Korle-Bu Teaching Hospital) and 50 healthy non-diabetic controls, were involved. Plasma glucose concentration was measured by the glucose-oxidase method. Fasting blood glucose was performed on all subjects except for the individuals with a history of T2DM. Hp genotype was determined by allele specific polymerase chain reaction (PCR). PCR produced Hp genotype-specific bands for the Hp1F, Hp1S, and Hp2 alleles. Statistical analyses revealed a significant difference in the Hp genotype distribution between diabetics and non-diabetics (χ 2 = 7.84, df = 2, p = 0.0198). Hp1-1 was the most frequent genotype among non-diabetics (58%) whilst Hp2-2 (38%) was most frequent genotype among diabetics. Majority of the diabetics were found in the Hp1S-1F and Hp2-2 genotype groups for diastolic BP (mmHg), systolic BP (mmHg) and FBG (mM). There was a strong association between DM and Hp2-2 genotype, followed by Hp2-1 (Hp1F-2 > Hp1S-2) with the least being Hp1-1 (Hp1F-1F, Hp1S-1F, Hp1S-1S). The risk of developing diabetes among people with Hp2-2 and Hp1F-2 genotypes was high. They can therefore be used as markers for an individual developing DM.