show Abstracthide AbstractMetagenomic sequencing is poised to revolutionise clinical microbiology, especially for identifying pathogens and predicting antimicrobial resistance (AMR) in bloodstream infections. Our study presents a direct-from-blood culture sequencing method that delivers results rapidly and accurately. In randomised testing of 273 blood samples (211 positive, 62 negative), we achieved 97% sensitivity and 94% specificity, which improved to 100% upon re-evaluation of plausible infections. Importantly, we detected 18 additional infections—including 13 polymicrobial and 5 previously unidentifiable—and delivered findings in just 3 hours and 30 minutes, nearly a third of time taken by routine methods. For the top ten pathogens, our method offered AMR results 20 hours quicker, with 88% sensitivity and 93% specificity. Specifically, for Staphylococcus aureus and Escherichia coli, sensitivity was 100% and 91%, with specificities of 99% and 94% respectively. These findings suggest the potential of integrating clinical metagenomics into standard diagnostics for faster and more comprehensive pathogen detection.