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OBJECTIVE Some studies have examined the association between dietary factors and risk of knee osteoarthritis (OA). We aimed to examine the prospective association of major dietary patterns with the risk of developing knee OA. METHOD We followed 2,842 participants in Osteoarthritis Initiative (OAI) aged 45 to 79 years and with at least one knee free from radiographic knee OA at baseline for up to 72 months. We defined knee OA incidence as Kellgren and Lawrence grade ≥ 2 during follow-up visits. Using principal component analysis, Western and prudent dietary patterns were derived. Cox proportional hazards models were used to assess the association between dietary patterns and incident knee OA. RESULTS Among study participants, 385 (418 knees) developed knee OA within 72 months. Following a Western dietary pattern was associated with an increased risk of knee OA (HR quartile 4 vs 1 = 1.69, 95% CI: 1.13 to 2.52, p trend: 0.03), while adherence to the prudent pattern was associated with a reduced risk of knee OA (HR quartile 4 vs 1 = 0.70, 95% CI: 0.50 to 0.98, p trend: 0.05). The observed associations attenuated after additionally adjusting for body mass index (BMI). The observed associations were mediated through BMI by approximately 30%. CONCLUSION Following a Western diet was associated with increased risk of knee OA, whereas following a prudent pattern was associated with a reduced risk of knee OA. The associations were partially mediated through BMI.