Abstract: Elastic anisotropy of shales is critical to accurate constraints for rock physical models, quantitative interpretation and hydraulic fracturing. However, the causes of elastic anisotropy of shales are very complicated, and the understanding of how multiple influence factors affect the elastic anisotropy of shales is still not clear. Hence, the orthogonal experiment, as an effective multiple factors experimental method, is adopted in this study to analyze the effect of multiple factors for shale elastic anisotropy. Three factors, clay content, organic matter (OM) content and compaction stress are selected as independent variables, the orthogonal test table L16(43) with four levels for each factor is adopted. According to the designed orthogonal table, sixteen artificial shales are constructed based on the cold-pressing method, and all the dry artificial shales are measured by the ultrasonic measurements. The influence of each factor on the elastic anisotropy and the sensitivity orders of three factors are obtained using the range analysis. The orders of sensitivity for selected factors follow the sequence clay content > compaction stress > OM content for velocity anisotropy parameters. The compaction mechanism of artificial shales is also discussed by the compaction factor, which are positively correlated with the velocity anisotropy parameters. The clay platelets orientation distribution function (ODF) of samples is evaluated by a theoretical model, the ODF coefficients are significantly affected by the clay content and compaction stress, and W200 are much more sensitive to these factors than W400. The results can provide a critical rock physics basis for quantitative interpretation and reservoir prediction of the low-maturity or maturity shale reservoir.