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The development of new refinement strategies for laboratory mice is a challenging task that contributes towards fulfilling the 3R-principle (Replacement, Reduction, Refinement) of laboratory animal science. In 3R – discussions, the main emphasis of interest is often on replacement and reduction as these two aspects may lead to a decrease of the laboratory animal number. But even with the best efforts, there are thousands of animals that are integral parts of research. Research in the field of refinement substantially benefits those animals still kept for scientific purposes. This study focuses on a cognitive enrichment program for laboratory mice. The Directive 2010/63 points out that the “establishments shall set up habituation and training programmes suitable for the animals” (Article 3.7). In accordance with that, it has been shown that handling programs can efficiently decrease anxiety towards the investigator in laboratory rodents. The goal of this study is to introduce clicker training for mice as a specific handling program. Clicker training is a form of positive reinforcement training using a conditioned secondary reinforcment – the click sound of a clicker – to be very accurate in strengthening a specific behaviour. Clicker training is well known from the field of companion animals and has made its way into laboratory animal science where it has been successfully implemented with laboratory monkeys. By introducing clicker training into the keeping of mice, we enable mice to experience a cognitive enrichment. Enhancing the ability of mice to cope successfully with environmental challenges contributes to their welfare. By developing a reliable protocol that is easily integrated into the daily routine of keeping laboratory mice, we can significantly improve the mice’s life-time experience of welfare. Those animals can efficiently profit from intense research in the field of refinement.