Background <p>Prevailing dietary guidelines recommend replacing saturated fatty acids (SFAs) with unsaturated fatty acids (USFAs). However, the relationship between specific types of SFA consumption and the risk of incident diabetes in China remains unclear.</p> Methods <p>We analyzed data from 15,021 apparently healthy Chinese adults, aged ≥ 20&#xa0;years, participating in the China Health and Nutrition Survey (CHNS). Cumulative averages of SFA intake were calculated using 3-day, 24-h dietary recalls from each survey cycle. Multivariable Cox proportional hazard models were employed to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for diabetes risk associated with isocaloric substituting carbohydrate or PUFAs with SFAs.</p> Results <p>Over 167,698 person-years of follow-up, 1014 incident diabetes were identified. After adjustment&#xa0;for multiple variables, isocaloric substitution of carbohydrates with total SFAs was associated with a lower risk of diabetes (P &lt; 0.001 for trend). The HR (95% CI) among the highest quartile of SFA intake individuals compared to the lowest quartile was 0.56 (0.40–0.79) for even-chain SFAs and 0.53 (0.37–0.76) for long-chain SFAs. Specifically, an inverse association with diabetes risk was observed for isocaloric substituting carbohydrates with lauric acid (12:0) [HRs for increasing quartiles (95% CIs): 0.62 (0.47–0.82), 0.62 (0.44–0.86), and 0.36 (0.24–0.53); P &lt; 0.001 for trend]. No significant association were found between diabetes risk and isocaloric substitutions of carbohydrates with myristic acid (14:0), palmitic acid (16:0), or stearic acid (18:0). Alternations of PUFAs with total SFAs or subtypes of SFAs present similar results.</p> Conclusions <p>Isocaloric substituting carbohydrates with lauric acid (12:0) was associated with a lower risk of incident diabetes. Given the strong correlation between lauric acid and diabetes, further research is needed to clarify the association and underlying mechanisms.</p>