Background: A significant proportion of Prostate cancer (PrCa) risk is attributable to heritable risk factors of which only a minority are high risk Mendelian traits. A greater proportion of PrCa is due to the combined effect of multiple low risk variants. There have been approximately 170 single nucleotide polymorphisms (SNPs) identified that are associated with PrCa risk in Europeans. Although each of these confer a low to moderate risk of PrCa, the cumulative risk (polygenic risk score, PRS) of increasing numbers of these risk alleles may confer a substantial relative risk. In PrCa genetic profiling, using PRS, could be used to target population screening to those at highest risk. BARCODE1 is the first study to prospectively review the use of a genetic profile in PrCa screening in the general population in the UK. Methods: Our study invited healthy males aged 55-69 to participate through their Primary Care physicians. Collection kits were mailed to retrieve saliva samples. Genotyping was carried out after DNA extraction using a study specific assay and the PRS was calculated for each participant using the sum of weighted alleles for 130 risk loci. Prostate MRI and Biopsy were then offered to men in the top 10% of the genetic risk profile. Results: 40,292 men were invited by letter to participate. The uptake was 22%, of whom 91% of men were eligible for inclusion. Following DNA extraction, genotyping, and quality control checks, data were available for 5008 men. 573 participants had PRS in the top 10% and were invited for screening; 180 underwent a prostate MRI, and 100 went on to have a systematic +/- targeted prostate biopsy. There were 42 diagnoses of PrCa (42%). 52% of cancers detected were low-risk and are being managed with Active Surveillance (AS). Conclusions: The early data from BARCODE1 have shown the feasibility of this population-based study, with an overall uptake of 22% and a cancer incidence of 42% of men in the top decile of PRS. We have identified clinically significant PrCa in 48%. The BARCODE1 study results will be important in defining the role of PRS genetic profiling in targeted PrCa population screening. Clinical trial information: NCT03857477.