OBJECTIVE: To investigate the associations between serum uric acid (UA) trajectories and the risk of metabolic dysfunction-associated steatotic liver disease (MASLD) in large cohort survey 2019-2021. METHODS: This cohort health survey included 11,644 participants without MASLD before January 1, 2021. Among them, 5578 (47.90%) were men and 6066 (52.10%) were women. The group-based trajectory model method was applied to identify serum UA trajectories from January 1, 2019, to December 30, 2021. New-onset MASLD events in 2021 were treated as outcomes. A logistic regression model was used to assess associations between UA trajectories and incidence of MASLD. RESULTS: Four distinct serum UA trajectories among both sexes were identified: "low-stable" trajectory 1 (n = 783 men
n = 1143 women), "moderate-moderate increasing" trajectory 2 (n = 2794 men
n = 3266 women), "moderate high-moderate increasing" trajectory 3 (n = 1660 men
n = 1464 women), and "high-increasing" trajectory 4 (n = 341 men
n = 193 women). During the 3-year follow-up period, 840 (15.06%) men and 408 (6.72%) women developed MASLD, respectively. Compared with the trajectory 1 group, the trajectory 4 group had the highest risk (odds ration [OR] 2.99 [95% confidence interval {CI} 1.70, 5.24] for men
OR 2.37 [95% CI 1.04, 5.33] for women), followed by the trajectory 3 (OR 2.23 [95% CI 1.52, 3.30] for men
OR 2.37 [95% CI 1.45, 3.92] for women) and trajectory 2 (OR 1.43 [95% CI 1.07, 1.94] for men
OR 1.37 [95% CI 0.93, 2.03] for women) groups. CONCLUSIONS: High serum UA trajectories were independent risk factors for MASLD in both sexes, which is critical for informing prevention and treatment strategies in public health initiatives and clinical practice.