Debridement, antibiotics and implant retention (DAIR) is the treatment of choice for acute postoperative and acute hematogenous periprosthetic joint infection (PJI). There is limited literature on predictive prognostic factors for DAIR. We aim to report the outcomes of DAIR and investigate the predictive prognostic factors. We retrospectively reviewed 106 DAIRs. Failure was defined as requiring removal of TKA implants. Predictive factors that may influence success of DAIR treatment such as age, gender, body mass index, ethnicity, American Society of Anesthesiologists score, comorbidities, preoperative erythrocyte sedimentation rate (ESR) and C-reactive protein, symptom duration, time between total knee arthroplasty and DAIR, cultures, rifampicin use, polyethylene liner change, and antibiotic duration were analyzed. The success rate of DAIR was 69.8% (74/106 patients). For successes, mean time from DAIR-to-mortality was longer than failures (61.6 ± 42.7 vs 9.75 ± 9.60 months, P = .0150). Methicillin-susceptible Staphylococcus aureus PJI (odds ratio OR 3.64, confidence interval CI 1.30-10.2, P = .0140) was a significant predictor for failure of DAIR. Higher preoperative ESR correlated to failure (OR 1.02, CI 1.01-1.04, P = .008). In successes, mean ESR was 75.4 (66.1-84.6), whereas mean ESR in failures was 116 (88.3-143) (P = .011). An ESR > 107.5 predicted failure with a sensitivity of 51.5 and specificity of 85.2. ESR > 107.5 correlated to failure (OR 6.60, CI 2.29-19.0, P < .001). Repeat DAIRs were strongly correlated to failure (OR 5.27, CI 1.99-13.9, P < .01). DAIR failure is associated with earlier time to mortality. Repeat DAIRs, elevated ESR > 107.5, and S aureus PJI are associated with treatment failure and 2-stage revision is recommended.