Background/Objectives: One-stage revision has become an increasingly accepted strategy for the treatment of chronic periprosthetic joint infection (PJI) of the knee in carefully selected patients. The use of a resorbable defensive antibacterial coating (DAC® hydrogel) represents an attractive adjunct to reduce bacterial adhesion and biofilm formation on revision implants. However, evidence regarding its long-term performance remains limited. Methods: We retrospectively reviewed 52 consecutive patients undergoing one-stage revision for knee PJI or infected spacer between 2014 and 2023 using a standardized surgical and antimicrobial protocol including local application of DAC hydrogel loaded with vancomycin alone or vancomycin plus meropenem. Clinical, microbiological and radiographic outcomes were evaluated. Infection-free survival was assessed using Kaplan–Meier analysis. Results: Forty-eight patients underwent revision for PJI and four for septic spacers. Four patients were unavailable for final evaluation. At mean follow-up of 7.0 ± 2.7 years (range 3–11 years), no infection recurrence was obtained in 47 of 48 clinically evaluable patients, corresponding to an infection-free survivorship of 97.9% at final follow-up. Mean Knee Society Score improved from 47.7 to 84.4 points, while functional KSS improved from 41.9 to 82.9 points. Pain at rest decreased from 6.9 to 0.7 and pain during movement from 8.1 to 1.6 on the visual analogue scale. Conclusions: This series represents, to our knowledge, the longest reported follow-up of one-stage knee revision using DAC antibacterial hydrogel. The favorable results obtained using hybrid fixation, with cemented epiphyseal fixation combined with uncemented stems coated with antibiotic-loaded DAC hydrogel, further expand the potential indications for this strategy. Larger comparative multicenter studies are warranted to confirm these findings.