PURPOSE: Little research has investigated the correlation of changes in long-term apolipoprotein B/apolipoprotein A-I (ApoB/ApoA-I) ratio with risk of new-onset type 2 diabetes (T2D) among ordinary people. Therefore, the research took long-term ApoB/ApoA-I ratio trajectories as independent variables for exploring their association with the risk of newly diagnosed T2D. METHODS: Altogether 5362 non-diabetic participants with a median age of 49 were enrolled in the cohort study. Their ApoB/ApoA-I ratio trajectories from 2016 to 2019 were analyzed and grouped using group-based trajectory modeling. The Kaplan-Meier approach was employed for calculating the newly diagnosed T2D-related incidence with different ApoB/ApoA-I ratio trajectories. A log-rank test was conducted for testing the presence of statistical difference in new-onset T2D incidence among the different ApoB/ApoA-I ratio trajectory groups. A multivariate Cox proportional hazards regression model was adopted for analyzing how ApoB/ApoA-I ratio trajectory changes affected new-onset T2D. RESULTS: From 2016 to 2019, 199 patients developed T2D (3% in 3 years). The incidence of T2D was 2.0%, 3.28%, 5.86%, and 6.92% for low, middle, upper, and high ApoB/ApoA-I ratio trajectories, respectively. Following adjustment of underlying confounding factors, in contrast to low ApoB/ApoA-I ratio trajectory, new-onset T2D risk ratios and hazard ratio (HR) (95% confidence intervals [CI]) for the middle lower ApoB/ApoA-I ratio trajectory, and upper middle and high ApoB/ApoA-I ratio trajectories were [HR (95% CI)] 1.35(0.88-2.08), 1.98(1.27-3.09) and 2.42(1.35-4.34), respectively, indicating high and statistically significant risks of T2D. CONCLUSION: Variations of the ApoB/ApoA-I ratio trajectory exerted independent effects on the 3-year incidence of T2D. Long-term monitoring on the ApoB/ApoA-I ratio locus may help improve the identification on patients with T2D.