Septic arthritis of the knee is encountered on a regular basis by orthopedists and nonorthopedists. No established therapeutic algorithm exists for septic arthritis of the knee, and there is much variability in management. This study assessed the number of surgical procedures, arthroscopic or open, required to eradicate infection. The study was a retrospective analysis of 79 patients who were treated for septic knee arthritis from 1995 to 2011. Patients who were included in the study had native septic knee arthritis that had resolved with treatment consisting of irrigation and debridement, either open or arthroscopic. Logistic regression analysis was used to explore the relation between the interval between onset of symptoms and index surgery and the use of arthroscopy and the need for multiple procedures. Fifty-two patients met the inclusion criteria, and 53% were male, with average follow-up of 7.2 years (range, 1-16.2 years). Arthroscopic irrigation and debridement was performed in 70% of cases. On average, successful treatment required 1.3 procedures (SD, 0.6; range, 1-4 procedures). A significant relation (P=.012) was found between time from presentation to surgery and the need for multiple procedures. With arthroscopic irrigation and debridement, most patients with septic knee arthritis require only 1 surgical procedure to eradicate infection. The need for multiple procedures increases with time from onset of symptoms to surgery.