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Introduction: Data on out-of-hospital cardiac arrest (OHCA) is limited in Italy, and there has never been a comprehensive systematic appraisal of the available evidence. Therefore, this review aims to explore the incidence, characteristics, and outcome of OHCA in Italy. Methods: We systematically searched PubMed, Embase, Google Scholar, ResearchGate, and conference proceedings up to September 23, 2022. Studies investigating OHCA in Italy and reporting at least one outcome related to cardiac arrest were considered eligible. The primary outcome was survival at the longest follow-up available. Risk of bias was assessed using the Joanna Briggs Institute critical appraisal tool. A random-effects model proportion meta-analysis was performed to calculate the pooled outcomes with 95% confidence interval (CI). Results: We included 42 studies (43,042 patients) from 13 of the 20 Italian regions published between 1995 and 2022. Only five studies were deemed to be at low risk of bias. The overall average incidences of OHCA attended by emergency medical services and with resuscitation attempted were 86 (range: 10–190) and 55 (range: 6–108) per 100,000 populations per year, respectively. Survival at the longest follow-up available was 9.0% (95% CI, 6.7–12%; 30 studies and 15,195 patients) in the overall population, 25% (95% CI, 21–30%; 16 studies and 2,863 patients) among patients with shockable rhythms, 28% (95% CI, 20–37%; 8 studies and 1,292 patients) among the Utstein comparator group. Favourable neurological outcome was 5.0% (95% CI, 3.6–6.6%; 16 studies and 9,675 patients). Return of spontaneous circulation was achieved in 19% (95% CI, 16–23%; 40 studies and 30,875 patients) of cases. Bystanders initiated cardiopulmonary resuscitation in 26% (95% CI, 21–32%; 33 studies and 23,491 patients) of cases but only in 3.2% (95% CI, 1.9–4.9%; 9 studies and 8,508 patients) with an automated external defibrillator. The mean response time was 10.2 (95% CI, 8.9–11.4; 25 studies and 23,997 patients) minutes. Conclusions: Survival after OHCA in Italy occurred in one of every ten patients. Bystanders initiated cardiopulmonary resuscitation in only one-third of cases, rarely with a defibrillator. Different areas of the country collected data, but an essential part of the population was not included. There was high heterogeneity and large variation in outcomes results and reporting, limiting the confidence in the estimates of incidence and outcome. Creating and maintaining a nationwide registry is a priority.