Amplicon sequencing is the workhorse of much microbiome research. But the sheer volume of data involved creates many opportunities for error and often requires access to both strong bioinformatics skills and large computational resources. These factors have motivated a team of researchers to develop LotuS2 (Less OTU Scripts 2). LotuS2 is a lightweight, user-friendly pipeline designed to increase the quality of amplicon sequencing data analysis. One way LotuS2 achieves this is by using a relatively strict read filter during the sequence clustering step. This filter produces "high-quality reads" using 21 quality filtering metrics, implements probabilistic and Poisson binomial read filtering, and filters out reads that can’t be dereplicated. Reads considered “mid-quality” are partly recovered later in the pipeline to further improve estimates of taxon abundance. LotuS2 (green) outperformed other popular pipelines, including mothur, PipeCraft2, QIIME 2, DADA2, and LotuS1, on three independent gut and soil datasets. as well as in a mock community. On average, LotuS2 was 29 times faster and could better reproduce the diversity of technical samples. Quick and easy to use, LotuS2 offers a powerful new tool for use in amplicon sequencing. The LotuS2 pipeline can be accessed at http://lotus2.earlham.ac.uk/