BACKGROUND AND AIMS: Cardiometabolic multi-morbidity (CMM) has emerged as a global healthcare challenge with a high mortality risk. This study aimed to explore the association between serum uric acid to high-density lipoprotein cholesterol ratio (UHR) and the incidence of CMM. METHODS AND RESULTS: We enrolled 8188 individuals in the CHARLS database. Multivariable cox proportional hazards regression, logistic regression, and restricted cubic splines (RCS) analysis were conducted to evaluate the association between UHR and CMM. During a median 109 months of follow-up, 858 (10.5 %) participants were identified with new-onset CMM. The incidences of CMM among participants in quartiles (Q) 1-4 of UHR were 7.57 %, 9.18 %, 10.75 %, and 14.41 %, respectively. A fully adjusted Cox model showed a higher UHR was significantly associated with an increased risk of CMM. Compared to participants in Q1 of UHR, the hazard ratios (HRs) (95 % confidence intervals [CIs]) using cox proportional hazards regression analysis for those in Q2-4 were 1.33 (1.05-1.68), 1.62 (1.29-2.04), and 2.14 (1.71-2.68), respectively. Additionally, the odds ratios (ORs) (95 % CIs) using multivariate logistic regression analysis for participants in quartiles 2 to 4 were 1.38 (1.07-1.78), 1.69 (1.32-2.16), and 2.34 (1.82-3.00), respectively, when compared to participants in Q1 of UHR. RCS analysis revealed a significant nonlinear association between UHR and CMM (nonlinear P <
0.05). CONCLUSION: A higher UHR was closely associated with an increased risk of CMM. Further studies on UHR could be beneficial for preventing and treating CMM.