Abstract Motivation Current read-mapping software uses a singular specification of alignment parameters with respect to the reference. In the presence of varying reference structures (such as the repetitive regions of the human genome), alignments can be improved if those parameters are allowed vary. Results To that end, the C++ program ProDerAl was written to refine previously generated alignments using varying parameters for these problematic regions. Synthetic benchmarks show that this realignment can result in an order of magnitude fewer misaligned bases. Availability and implementation *Nix users can retrieve the source from GitHub (https://github.com/Benjamin-Crysup/proderal.git). Windows binary available at https://github.com/Benjamin-Crysup/proderal/releases/download/v1.1/proderal.zip. Supplementary information Supplementary data are available at Bioinformatics online.