Integrating single cell RNA-seq profiles is posing new challenges as datasets are rapidly expanding, now with over 100 million cells in the public domain. We present the latest version of the Harmony integration software, which efficiently scales to >100M cells and >1K datasets without specialized hardware. Moreover, optimizations to the underlying algorithm help prevent overintegration in biologically heterogeneous datasets. Harmony2 enables efficient, accurate integration of large, complex single-cell atlases.