Objective Respiratory syncytial virus (RSV) is a common respiratory pathogen not only in children, but also in adults. Country-specific data on the epidemiology and burden of disease are essential for policy decisions. In view of a recent authorization of adult RSV vaccines, we aimed to comprehensively collect and assess evidence on the epidemiology and burden of RSV in Italian adults. Methods A systematic literature review was conducted according to the available guidelines. Random-effects proportional meta-analysis was performed to obtain pooled estimates and the observed heterogeneity was investigated by using both subgroup and meta-regression analyses. Results A total of 35 studies were identified. RSV seasonal attack rates ranged from 0.8 ‰ in community-dwelling older adults to 10.9% in hematological outpatients. On average, 4.5% (95% CI: 3.2-5.9%) of respiratory samples tested positive for RSV. This positivity prevalence was higher in older adults (4.4%; 95% CI: 2.8-6.3%) than in working-age adults (3.5%; 95% CI: 2.5-4.6%) and in outpatient (4.9%; 95% CI: 3.1-7.0%) than inpatient (2.9%; 95% CI: 1.5-4.8%) settings. Study location and sample size were also significant predictors of RSV detection frequency. The pooled estimate of in-hospital mortality was as high as 7.2% (95% CI: 4.7-10.3%). However, other important indicators of the diseases burden, such as complication and hospitalization rates, are missing. Conclusion RSV poses a measurable burden on Italian adults, especially those of older age and with some co-morbidities. Policy makers should give priority to health technology assessment of the novel RSV vaccines.