We examined the association between previously reported modifiable risk factors for accelerated knee osteoarthritis (AKOA) at the Osteoarthritis Initiative's (OAI) baseline and 48-month visits among adults who develop AKOA between the 48- and 96-month visits. We conducted a case-control study using data from the OAI baseline to the 96-month visit. Participants had no radiographic knee osteoarthritis (KOA) in the index knee at OAI baseline and 48-month visits [Kellgren-Lawrence (KL) <2]. We classified 2 groups: (1) AKOA: >1 knee developed advance-stage KOA (KL = 3 or 4) between 48- and 96-month visits and (2) No KOA: no KOA and no change in radiographic severity bilaterally over 96 months. We used logistic regression models to evaluate the association between the outcome of AKOA (versus no KOA) and several modifiable risk factors collected at OAI baseline and 48-month visits [body mass index (BMI), systolic blood pressure, comorbidity score, and NSAID use]. We also explored a new injury from baseline to 48 months and from 48- to 96 months. Adults with greater baseline and 48-month BMI were more likely to develop AKOA. Injury was only associated with AKOA onset when it occurred within 4 years of developing AKOA [prior 2 years: odds ratio = 6.21; 95% confidence interval (CI) 3.40, 11.35; 2-4 years prior: odds ratio = 4.42, 95% CI 2.06, 9.50]. BMI may consistently predispose an adult to AKOA, but certain injuries are likely a catalyst for AKOA.