Misophonia is a clinical syndrome which is characterized by intense emotional and physical reactions to idiosyncratic sounds. However, its psychometric measurement is still in the early stages. This study describes the optimization of a self-report instrument, the Berlin Misophonia Questionnaire (BMQ), and addresses its strengths in comparison to existing psychometric measures. This new measure integrates contemporary empirical findings and is based on the latest criteria of misophonia. A cross-sectional online study was conducted using data of 952 affected as well as non-affected individuals. The final BMQ-R consists of 77 items in 21 scales, which were selected using a probabilistic item selection algorithm (Ant Colony Optimization). The results of confirmatory factor analyses, the assessment of reliability, and an extensive construct validation procedure supported the reliability and validity of the developed scales. One outstanding strength of the BMQ-R is its comprehensive measurement of misophonic emotional and physical responses. The instrument further allows for distinguishing between behavioral, cognitive, and emotional dysregulation; the measurement of clinical insight and significance; as well as discerning reactive and anticipating avoidance strategies. Our work offers several improvements to the measurement of misophonia by providing a reliable and valid multidimensional diagnostical instrument. In line with the scientific consensus on defining misophonia, the BMQ-R allows to formally recognize individuals with misophonia and so to compare findings of future studies. Undoubtedly, this measure fills a research gap, which we hope will facilitate the investigation of causes and treatment of misophonia.