Crinum macowanii has been used extensively in traditional medicines for treatment of various illnesses such as oedema and ‘heart disease’. Previous studies of the crude bulb extracts on Langendorff perfused isolated rat hearts indicated a positive inotropic effect. The aim of this study was to isolate and characterize compound(s) from C. macowanii with cardiovascular effects similar to that observed with the crude extracts of the plant. The methanol extract of dried bulbs was extracted for alkaloids, and structural elucidation of the isolated alkaloid identified it as hippadine. The cardiovascular effects of hippadine was evaluated in vitro in isolated perfused rat hearts using the “double sided” working heart system. Perfusion with 0.5 μg/ml and 5.0 μg/ml hippadine in Krebs-Hanseleit buffer led to significant decreases in coronary flow, aortic output, cardiac output, systolic pressure, and heart rate, accompanied by increases in diastolic pressure. Hippadine exhibited a negative chronotropic and inotropic effect on the isolated rat heart and is responsible either partly or fully for the cardiovascular effects of C. macowanii.