Regional differences in the mural structure of the coronary sinus are important in understanding its physico-mechanical properties and the basis for extent of atrial fibrillation and ablation. These features are only scarcely reported. This study therefore aimed at describing regional differences in the mural structure of coronary sinus among black Kenyans. This was a descriptive cross-sectional study on coronary sinuses from fifteen hearts obtained during autopsy on adult black Kenyans at the Department of Human Anatomy, University of Nairobi. Five-millimeter-long specimens were taken from the proximal, middle and terminal segments of the coronary sinus and processed routinely for paraffin embedding and sectioning. Seven-micron thick sections were stained with Masson’s Trichrome to demonstrate connective tissue and smooth muscle while Weigert’s Resorcin Fuschin stain was used to demonstrate elastic fibres. The slides were examined with a light microscope and photomicrographs taken with a high resolution digital camera. The results are presented in micrographs. The wall comprised three layers namely internal, middle and external. Regional differences were observed in the middle layer. In the proximal segment, there were concentrically oriented smooth muscles scattered within connective tissue. The middle and terminal segments on the other hand comprised cardiac muscle oriented both concentrically and longitudinally. The muscle was separated by connective tissue rich in elastic fibres and abundant vasa vasora. The external layer comprised connective tissue. In conclusion the middle layer of the wall of the coronary sinus displays regional differences. The smooth muscle at the proximal segment may confer contractility to enhance blood flow while the cardiac muscle in the other segments enables it to function in synchrony with the right atrium during atrial systole. The complex arrangement of circular and longitudinal muscle facilitates blood flow and may also constitute a sphincter mechanism.Keywords: Coronary sinus, regional differences, smooth and cardiac muscl