Introduction <p>microbiological eradication after two-stage revision is not obtained in up to 18% of cases, yet the prognostic value of positive cultures at reimplantation remains controversial. The primary aim of the study was to evaluate outcomes of patients with positive cultures at second stage, identifying failure predictors. The secondary outcome was to compare reintervention-free survival.</p> Materials and methods <p>this retrospective cohort study included patients treated using a two-stage protocol between 2016 and 2022. PJI was diagnosed using MSIS 2013 criteria, and treatment failure was defined according to a Delphi-based consensus. Cox regression analysis was employed to assess risk factors for failure, including Charlson Comorbidity Index (CCI); American Society of Anesthesiologists (ASA) score; age; time to reimplantation; joint; number of previous septic revisions; positive cultures number at reimplantation; a difficult to treat organism.</p> Results <p>83 cases were reviewed (63 hips, 20 knees). The average interval between stages was 181 days. Over 6 years follow-up (FU), elevated BMI was the only significant predictor of failure (HR 1.19; 95% CI 1.02–1.39; <i>p</i> = 0.03). In contrast, positive cultures at reimplantation were not associated with an increased failure risk (<i>p</i> = 0.95), even in cases with multiple positive cultures (<i>p</i> = 0.72).</p> Conclusions <p>elevated BMI at reimplantation was independently associated with subsequent failure. Clinical outcomes were not significantly associated with the presence or number of positive cultures, although smaller effects cannot be excluded given the limited sample size. These findings emphasize the importance of a patient-focused rather than culture-centered approach.</p> Level of evidence <p>III.</p>