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This study presents the evaluation of a computer-based learning program for children with developmental dyscalculia and focuses on factors affecting individual responsiveness. The adaptive training program Calcularis 2.0 has been developed according to current neuro-cognitive theory of numerical cognition. It aims to automatize number representations, supports the formation and access to the mental number line and trains arithmetic operations as well as arithmetic fact knowledge in expanding number ranges. Sixty-seven children with developmental dyscalculia from second to fifth grade (mean age 8.96 years) were randomly assigned to one of two groups (Calcularis group, waiting control group). Training duration comprised a minimum of 42 training sessions à 20 min within a maximum period of 13 weeks. Compared to the waiting control group, children of the Calcularis group demonstrated a higher benefit in arithmetic operations and number line estimation. These improvements were shown to be stable after a 3-months post training interval. In addition, this study examines which predictors accounted for training improvements. Results indicate that this self-directed training was especially beneficial for children with low math anxiety scores and without an additional reading and/or spelling disorder. In conclusion, Calcularis 2.0 supports children with developmental dyscalculia to improve their arithmetical abilities and their mental number line representation. However, it is relevant to further adapt the setting to the individual circumstances.