We describe the synthesis and positive inotropic evaluation of a series of 2-(4-substitutedbenzylpiperazin-1-yl)-N-(2-oxo-2,3-dihydrobenzooxazol-6-yl)acetamides by measuring left atrial stroke volume in preparations of isolated rabbit hearts. Several compounds were developed from and showed favorable activities compared with the standard drug milrinone. Compound 4l was the most potent with an increased stroke volume of 11.78 ± 0.18% (milrinone 6.36 ± 0.13%) at 1 × 10(-4) M in our in-vitro study. The chronotropic effects of compounds having inotropic effects were also evaluated.