Next-generation sequencing has become a routine tool for biology and medicine. However, eliminating errors in next-generation DNA sequencing has proved challenging. I am going to talk about our newly developed error-correction code (ECC) sequencing, a method to greatly improve sequencing accuracy by combining fluorogenic sequencing-by-synthesis (SBS) with an information theory–based error-correction algorithm. ECC embeds redundancy in sequencing reads by creating three orthogonal degenerate sequences, generated by alternate dual-base reactions. This is similar to encoding and decoding strategies that have proved effective in detecting and correcting errors in information communication and storage. We showed that, when combined with a fluorogenic SBS chemistry with raw accuracy of 98.1%, ECC sequencing provides single-end, error-free sequences up to 200 bp. I also will discuss the recent development we have made on the high-throughput instrumentation of this ECC sequencing approach. We have integrated millions of femtoliter reaction wells into a novel microfluidic platform and have built a prototype upon it to perform high-throughput sequencing experiments such as RNA-seq, non-invasive prenatal screen, and small copy number variation identification.