Purpose <p>Late acute haematogenous total knee arthroplasty (LAH TKA) infections represent approximately 20% of all prosthetic infections. Debridement, antibiotics, and implant retention (DAIR) is a widely accepted treatment; however, it carries a significant risk of failure. The study aims to identify risk factors for DAIR failure in LAH TKA infections, focusing on blood cultures (BC) as a potential contributor.</p> Methods <p>A retrospective cohort study was conducted on 37 cases of LAH TKA infections from 2015 to 2023. Patients were divided into two groups: 20 in the success group (SG) and 17 in the failure group (FG). The study analyzes various factors, including demographics, comorbidities, serum and joint fluid biomarkers, blood and intraoperative cultures, prior infection or antibiotic use, and surgical and post-surgical variables.</p> Results <p>Positive BC were more frequent in the FG compared with the SG (<i>P</i> = 0.03), and were also more common in patients with a history of prior infection (<i>P</i> = 0.03). Logistic regression identified positive BC as the only significant predictor of DAIR failure (odds ratio (OR) 12, 95% confidence interval (CI) 1.1–18, <i>P</i> = 0.04), even after adjusting for other variables. Positive intraoperative cultures were more frequent in the FG, particularly in those with a prior infection history (<i>P</i> = 0.08), even if they were receiving antibiotics (<i>P</i> = 0.05).</p> Conclusions <p>Positive BC may be an additional risk factor for DAIR failure in LAH TKA. This highlights the importance of routinely performing BC during diagnosis.</p> <p><i>Level of evidence:</i> level III.</p>