We retrospectively examined prospective data on the incidence and time to total knee replacement (TKR) in (1) patients with grade IV osteoarthritis (OA) treated with hylan G-F 20 from 1997 to 2010 (full cohort; 1,863 knees) and (2) a patient subset treated from 1997 to 2003 (original cohort; 1,187 knees) to determine any continued hylan G-F 20 influence on TKR delay. In both the cohorts, 25 to 28% knees underwent a TKR, with an average of 2.8 to 3.1 years occurring between hylan G-F 20 and surgery. Age was a significant predictor of time to TKR. Knee synovitis increased slightly with repeat courses; most cases considered mild or moderate. Survival analysis showed that TKR was delayed for > 7 years in 75% of 1,863 grade IV OA knees (1,342 patients) treated with hylan G-F 20 in an orthopedic practice. Consistent with our previous report (Waddell and Bricker, 2007), we show hylan G-F 20 continues to delay the need for TKR.