Pairwise sequence alignment has received a new motivation due to the advent of next-generation sequencing technologies, particularly so for the application of re-sequencing—the assembly of a genome directed by a reference sequence. After the fast alignment between a factor of the reference sequence and a high-quality fragment of a short read by a short-read alignment programme, an important problem is to find the alignment between a relatively short succeeding factor of the reference sequence and the remaining low-quality fragment of the read allowing a number of mismatches and the insertion of a single gap in the alignment. In this article, we present GapMis-OMP, a tool for pairwise short-read alignment that works on multi-core architectures. It is designed to compute the alignments between all the sequences in a first set of sequences and all those from a second one in parallel. The presented experimental results demonstrate that GapMis-OMP is more efficient than most popular tools.