BACKGROUND: Recently, the potential rehabilitation value of music has been examined and music-based interventions and techniques such as the Negative Mismatch (MMN) have been increasingly investigated in the neurological rehabilitation context. OBJECTIVE: The aim of this study was to investigate the effectiveness of a negative mismatch-based therapy on the disability and quality of life in patients with stroke in sub-acute phase. METHODS: Thirty patients with a stroke diagnosis in sub-acute phase were randomly assigned to one of two groups: Mismatch (Mg) or Control (CTRLg) group. Both groups used an innovative Android application: Temporal Musical Patterns Organisation (Te.M.P.O). The Disability Rating Scale (DRS), the Modified Barthel Index (MBI) and the Stroke Specific Quality of Life scale (SSQoL) were used at the baseline (T0) and after four weeks of training (T1), in order to assess changes over time. RESULTS: Statistical analysis was performed using the data of 24 (Mg = 12, CTRLg = 12) subjects. The results show a major improvement of the Mg with respect to the CTRLg in all clinical scales score. CONCLUSION: The temporal negative mismatch-based therapy performed with the Te.M.P.O. application could be useful in improving the disability and the quality of life in stroke survivors in a sub-acute phase.