It is challenging to acquire satellite sensor data with both fine spatial and fine temporal resolution, especially for monitoring at global scales. Among the widely used global monitoring satellite sensors, Landsat data have a coarse temporal resolution, but fine spatial resolution, while moderate resolution imaging spectroradiometer (MODIS) data have fine temporal resolution, but coarse spatial resolution. One solution to this problem is to blend the two types of data using spatio-temporal fusion, creating images with both fine temporal and fine spatial resolution. However, reliable geometric registration of images acquired by different sensors is a prerequisite of spatio-temporal fusion. Due to the potentially large differences between the spatial resolutions of the images to be fused, the geometric registration process always contains some degree of uncertainty. This article analyzes quantitatively the influence of geometric registration error on spatio-temporal fusion. The relationship between registration error and the accuracy of fusion was investigated under the influence of different temporal distances between images, different spatial patterns within the images and using different methods (i.e., spatial and temporal adaptive reflectance fusion model (STARFM), and Fit-FC; two typical spatio-temporal fusion methods). The results show that registration error has a significant impact on the accuracy of spatio-temporal fusion; as the registration error increased, the accuracy decreased monotonically. The effect of registration error in a heterogeneous region was greater than that in a homogeneous region. Moreover, the accuracy of fusion was not dependent on the temporal distance between images to be fused, but rather on their statistical correlation. Finally, the Fit-FC method was found to be more accurate than the STARFM method, under all registration error scenarios. © 2008-2012 IEEE.