Differential scanning calorimetry (DSC) is an invaluable tool for studying protein thermal denaturation. Currently, however, no software enabling complex analysis of the resulting thermograms in a user-friendly manner is available. To address this, we have developed MatLab-based software called CalFitter which allows fitting of DSC curves into 10 models of unfolding including different number of intermediates, reversible and irreversible transitions and their combination. Moreover, it allows simultaneous fitting of DSC scans together with re-heating traces collected after termination of the first run at different temperatures. CalFitter output can be exported to single excel file that includes quantitative description of unfolding model in terms of number of intermediates, energy parameters of each transition with statistical information and fraction of protein states calculated based on the model.