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Background: Several studies have reported a high prevalence of osteoarthritis (OA) of the knee among agricultural workers. We investigated work-related factors that increase the risk of knee OA among Korean farmers. Methods: Data were extracted from the Jeonnam Center for Farmer's Safety and Health survey, conducted between 2013 and 2015. The sample included 489 farmers (man 240, woman 249). We defined knee OA as radiographic knee OA (≥ Kellgren-Lawrence grade 2) with symptoms (≥ Western Ontario and McMaster Universities Osteoarthritis, Korean version score 29.5). We considered covariates such as cumulative squatting working time (CSWT), cumulative heavy lifting working time (CLWT), body mass index (BMI), and history of knee injury. Odds ratios (ORs) and their corresponding 95% confidence intervals (CIs) were calculated for knee OA and adjusted for relevant covariates. Results: The results of multivariate logistic regression analysis indicated that knee OA was correlated by factors such as sex, age, BMI, history of knee injury, CSWT, and CLWT. Particularly, CSWT > 20,000 hours (OR: 2.83; 95% CI: 1.35–5.92; reference < 10,000 hours) and CLWT > 5,000 hours (OR: 2.62; 95% CI: 1.14–6.06; reference < 2,000 hours) were associated with an increased risk of knee OA after adjustment for covariates. Conclusions: Squatting posture and heavy lifting associated with farm work might increase the risk of knee OA among Korean farmers.