The purpose of this study was to establish the reliability and validity of the Italian version of the Stroke Impact Scale 3.0 (SIS 3.0), a specific and multidimensional instrument that assesses quality of life (QOL) in stroke survivors. Forty-five patients treated in three Rehabilitation Hospitals of the Lazio Region were included in the study. Patients were assessed using the SIS 3.0, the SF-36, the Barthel Index, the Mini Mental State Examination, the Hospital Anxiety and Depression Scale, the NIH Stroke Scale, the Modified Rankin Scale, and the Instrumental Activities of Daily Living. Results showed good internal consistency of the SIS 3.0 (Cronbach's alpha 0.86-0.98), and a good test-retest reliability (r > 0.70, p < 0.000) except for the Emotion and Social Participation subscales. At the re-test, 15 days after the first administration, SIS 3.0 showed a good responsiveness to change, documenting clinical improvement in stroke survivors. Significant correlations between the other instruments and the SIS 3.0 allowed to establish the concurrent validity of the SIS 3.0. Although the small sample size the Italian version of the SIS 3.0 showed good internal consistency and test retest reliability, as well as validity and responsiveness to changes. Since the SIS 3.0 is a specific tool to measure QOL in stroke survivors, its Italian version could be successfully used also in Italian population to better identify predictors of QOL and evaluate the effectiveness of health interventions.