Sub-sampling pattern design for motion estimation in video compression. A motion estimation method divides a first frame into a plurality of macroblocks, performs block matching for a current macroblock pair on a candidate macroblock pair of a second frame. The current macroblock pair and the candidate macroblock pair are sampled according to a sub-sampling pattern, and an error measure between the current and candidate macroblock pairs is calculated. The sub-sampling pattern is constructed by a plurality of repeating units, and each repeating unit is composed of a first and a second pattern unit.