Abstract Background First-degree relatives of SADS victims (defined as a sudden death of a previously healthy individual where no cause can be found despite post-mortem examination) or individuals suffering an Unexplained Cardiac Arrest (defined as a sudden cardiac arrest with successful resuscitation where no cause can be found despite thorough investigation) are recommended to undergo clinical cardiac evaluation for potential inherited cardiac conditions (ICC). However, data on the yield of family screening in these populations remains scarce. Aim This study aimed to perform the first systematic review of the diagnostic yield of clinical screening of first-degree relatives of SADS or UCA probands. A secondary aim was to compare the diagnostic yield of adult-aged and paediatric-aged relatives. Methods The systematic review was prospectively registered on PROSPERO and was undertaken utilising PRISMA guidelines. The online databases Embase, Medline and Web of Science were searched for original articles published in English from 1946 to June 2023. Included studies described the clinical cardiac screening and diagnostic yield of first-degree relatives of SADS and UCA probands. Quality of selected studies were assessed using a modified Joanna Briggs Institute (JBI) checklist. Results 14 studies met the inclusion criteria, which together included 1646 first-degree relatives of SADS probands and 656 first-degree relatives of UCA probands. 11 out of the 14 studies were retrospective cohort studies and cohort size varied from 56 – 398 (median 108, IQR 82-215). Of those studies that reported follow up length (n=8), screening ranged from one-off clinical evaluation to serial clinical screening. Overall diagnostic yield described by included studies ranged from 0 – 25%. The combined mean diagnostic yield of SADS relatives was 11.7% ± 7.5. This did not differ significantly from that of relatives of UCA probands (6.9% ± 7.4) [p=0.246]. Three studies described outcomes of clinical screening in 235 paediatric relatives, with an overall reported yield of 9.4% ± 3.4, which is not significantly different to adult populations (10.4% ± 8.4 [p=0.849]). The most common diagnosis in relatives was Long QT Syndrome followed by Brugada Syndrome. Despite probands having no heart muscle phenotype on post-mortem or clinical evaluation, 22 relatives were diagnosed with a cardiomyopathy (9.3% of all diagnoses). Conclusion Whilst there is a clear indication for clinical screening of first-degree relatives for ICCs following a SADS death or an Unexplained Cardiac Arrest, a lack of well-designed large population-based studies means that the evidence base supporting when or how relatives should be screened is not robust. The diagnostic yield in reported literature varies considerably with no difference between SADS and UCA cohorts and a similar yield in paediatric and adult relatives. This supports systematic screening for all first-degree relatives regardless of age.PRISMA Flow Diagram