Transcription activator-like effector nucleases (TALENs) have become an accepted tool for targeted mutagenesis, but undesired off-targets remain an important issue. We present TALENoffer, a novel tool for the genome-wide prediction of TALEN off-targets. We show that TALENoffer successfully predicts known off-targets of engineered TALENs and yields a competitive runtime, scanning complete mammalian genomes within a few minutes.