The increasing and indiscriminate use of antibiotics and poor patient compliance have led to the development of bacterial resistance to antibiotics. The use of synergistic combinations in antimicrobial chemotherapy is often used commercially for the treatment of various infections. Traditional healers often use combinations of plants to treat or cure diseases. Vangueria spinosa Roxb. (Rubiaceae) is a deciduous shrub or small tree (height from 3-7 m,) depending upon the habitat. This plant has some medicinal value, an infusion of the roots and leaves is used to treat malaria, chest ailments like pneumonia, as a purgative and to treat ringworms, infusion of the leaves is used for the relief of toothache. For the treatment of swelling of the limbs the affected parts are bathed in a decoction of the pounded leaves and small twigs, especially in children (2,3). It also possesses some antibacterial property (4). In this study the antibacterial activity of V. spinosa ethanolic leaf extract was assessed in vitro when used alone and in combination with doxycycline and ofloxacin against one Gram-positive and three Gram-negative bacteria.