Various techniques for accelerating Smith-Waterman sequence alignments are provided. For example, threads in a group of threads are employed to use an interleaved cell layout to store relevant data in registers while computing sub-alignment data for one or more local alignment problems. In another example, specialized instructions that reduce the number of cycles required to compute each sub-alignment score are utilized. In another example, threads are employed to compute sub-alignment data for a subset of columns of one or more local alignment problems while other threads begin computing sub-alignment data based on partial result data received from the preceding threads. After computing a maximum sub-alignment score, a thread stores the maximum sub-alignment score and the corresponding position in global memory.