It is known that the interface of slurry displacement during cementing reflects the extent of two-phase fluid intermixing. A longer interface means that more displacing fluid becomes contaminated. When the interface becomes too long, it can occur that the trailing edge of the interface fails to reach a designed cementing segment at the end of operation, which reduces displacement effectiveness and adversely affects cementing quality and well integrity. In this paper, a 3D numerical model was developed and employed to analyze the effects of slurry density difference on the displacement interface in the eccentric annulus of horizontal wells. The simulation results showed that smaller density difference can create shorter interface and lead to better displacement efficiency when casing is centrally placed in a horizontal borehole. When the casing is eccentric, slurry tends to advance in the annular upper side under smaller density difference; otherwise, the opposite result will be obtained under greater density difference. Therefore, there exists an optimal density difference under which a minimum interface length can be achieved for a given casing eccentricity. In addition, the optimal density difference increases as the shear thinning index, consistency index and yield point of a cement slurry increase. In order to minimize the intermixing extent of two-phase fluids and slurry fingering effects in cementing operations, it is necessary to take into consideration the comprehensive influence of casing eccentricity, slurry density, and rheological parameters to design slurry parameters properly, which will achieve higher displacement efficiency and better cementing quality.