Hypertension and diabetes mellitus, two of the leading risk factors for atherosclerosis, are associated with numerous complications, including heart attacks and strokes. This study established the prevalence and determinants of isolated systolic hypertension (ISH) in diabetes mellitus patients visiting the Tamale Teaching Hospital. In this purposive cross-sectional study, 107 diabetes mellitus patients were recruited from the out-patient diabetes clinic of the Tamale Teaching Hospital (TTH). Blood and urine samples were collected for the estimation of fasting blood glucose (FBG) and routine urinalysis respectively. A well-structured pre-tested questionnaire was used to obtain socio-demographic data and clinical history of participants, and their blood pressure measured with a mercury sphygmomanometer. The prevalence of ISH among the participants was 37.4%. Mean age and FBG were significantly higher among participants with ISH than the normotensives (56.20 ± 10.60 v 48.44 ± 11.6, P= 0.022; and 8.80 ± 3.06 v 6.01 ± 0.50, P= 0.034 respectively). Type of diabetes mellitus was associated with ISH (P= 0.010) and age was a risk factor of ISH (OR= 1.057, P= 0.008). Isolated systolic hypertension was prevalent in 37.4% of diabetes mellitus patients and was associated with older age. Effective measures should, therefore, be instituted to prevent ISH in patients with type 2 diabetes especially the elderly.