Background: Septic arthritis after anterior cruciate ligament (ACL) reconstruction is a rare but severe complication. Treatment regimens differ, and optimal management has not been established. Purpose: To determine the incidence of postoperative infections after ACL reconstruction, to identify the microbiological spectrum, and to evaluate a standardized graft-retaining treatment protocol consisting of sequential arthroscopic irrigation and debridement (I&D) procedures and antibiotic therapy until C-reactive protein levels are within normal range. Study Design: Case series; Level of evidence, 4. Methods: From January 2004 to June 2014, a total of 7096 consecutive arthroscopic ACL reconstructions were performed at a single institution (5907 primary and 1189 revision reconstructions). Thirty-six cases with postoperative septic arthritis were identified and retrospectively analyzed with regard to incidence, clinical presentation, time to and number of arthroscopic reoperations, and microbiological findings. The follow-up examination consisted of a clinical examination, instrumeted measurement of laxity (KT-1000 arthrometer), classification according to objective and subjective International Knee Documentation Committee (IKDC) scores, and radiological evaluation. Results: The incidence of septic arthritis was 0.51% (n = 36), with 0.41% (n = 24) in primary and 1.01% (n = 12) in revision reconstructions (odds ratio, 2.5; P = .008). The first I&D was performed a mean (±SD) of 19.6 ± 10.6 days after the index procedure. Eradication was achieved in all patients after a mean of 2.25 ± 1.22 procedures, with graft retention in all but 1 patient (97.2%). The mean duration of antibiotic treatment was 5.4 ± 2.3 weeks (range, 2.1-12.9 weeks) and ≤4 weeks in 13 patients (36%). No recurrence of infections was seen. Coagulase-negative staphylococci (62.5%) and Staphylococcus aureus (21.9%) were the most frequent pathogens. Twenty-nine patients were available for follow-up (80.6%) after a mean 4.7 ± 3.2 years (range, 0.7-11.2 years). Two patients suffered recurrent nontraumatic ACL insufficiency (6.9%), and all others (93.1%) had an intact graft, with a mean KT-1000 arthrometer side-to-side difference of 1.4 ± 0.9 mm. The mean subjective IKDC score was 80.4 ± 11.2. No emergence or deterioration of osteoarthritis related to infections was seen. Conclusion: Postoperative septic arthritis is rare but serious after arthroscopic ACL reconstruction. Graft retention and good to excellent clinical results can be obtained with an arthroscopic treatment protocol. The duration of antibiotic therapy should be based on the individual course.