Pheniqs (Philology Encoder with Quality Statistics) is a fast high-throughput sequencing read classifier implemented in multi threaded C++ that has been used by the NYU Center for Genomics and Systems Biology core facility since December 2014. It provides both a traditional Hamming distance-based barcode decoder and a more accurate maximum likelihood decoder that consults priors and quality scores. Pheniqs can read and write sequencing data from FASTQ, SAM, BAM and CRAM file formats and report the barcodes as well as decoding confidence for individual reads in SAM auxiliary tags. A flexible syntax enables Pheniqs to address reads at arbitrary offsets from both the 5’ and 3’ end and handle complex experimental designs that included sample, cellular and molecular barcodes. Using the maximum likelihood decoder, Pheniqs outperforms similar tools in speed, flexibility and accuracy.