An open-source, cross-platform software aimed at conformer generation and unsupervised rigid-body molecular alignment is presented. Different algorithms have been implemented to perform single and multi-conformation superimpositions on one or more templates. Alignments can be accomplished by matching pharmacophores, heavy atoms or a combination of the two. All methods have been successfully validated on eight comprehensive datasets previously gathered by Sutherland and co-workers. High computational performance has been attained through efficient parallelization of the code. The unsupervised nature of the alignment algorithms, together with its scriptable interface, make Open3DALIGN an ideal component of high-throughput, automated cheminformatics workflows.