CD-HIT is a widely used program for clustering biological sequences to reduce sequence redundancy and improve the performance of other sequence analyses. In response to the rapid increase in the amount of sequencing data produced by the next-generation sequencing technologies, we have developed a new CD-HIT program accelerated with a novel parallelization strategy and some other techniques to allow efficient clustering of such datasets. Our tests demonstrated very good speedup derived from the parallelization for up to xe2x88xbc24 cores and a quasi-linear speedup for up to xe2x88xbc8 cores. The enhanced CD-HIT is capable of handling very large datasets in much shorter time than previous versions.