Abstract: It's a very efficient approach to produce food grade calcium acetate using wasted oysters shells by direct method. Single factor experiments and variance analysis of main factors were adopted to explore the action law and influence level for the content and yield of products between particle size of shell powder, shellacid ratio, water-shell ratio, reaction time and p H value. The process conditions was systemically optimized in virtue of multi-target orthogonal design. The experimental results were demonstrated that the main reaction was affected prominently by such three key factors including shell-acid ratio, water-shell ratio and reaction time. The optimum production conditions were determined as follows:shell-acid ratio was 0.75 ∶1, water-shell ratio was 21∶1 and reaction time was 140 min. Under the condition of above optimal parameters, the content and yield average of calcium acetate products achieved 99.63%, 93.72%, respectively. The research provided certain practical significance owing to outstanding quality and stable reliability of calcium acetate products after optimization.