The prevalence of hyperuricemia in Taiwan is high, and hyperuricemia has been associated with a risk of developing several diseases. Although the traditional risk factors for hyperuricemia are well known, the relationship between heavy metals and hyperuricemia is still undefined. Therefore, the aim of this study was to investigate the relationship between hyperuricemia and heavy metals. A total of 2447 participants (977 males and 1470 females) residing in southern Taiwan were enrolled, and levels of the following heavy metals were measured: lead in blood, and nickel, chromium, manganese, arsenic (As), copper, and cadmium in urine. Hyperuricemia was defined as a serum uric acid level greater than 7.0 mg/dL (416.5 μmol/L) in men and 6.0 mg/dL (357 μmol/L) in women. The participants were divided into two groups: those without hyperuricemia (n= 1821; 74.4%) and those with hyperuricemia (n= 626; 25.6%). Multivariate analysis showed that only high urine As (log per 1 μg/g creatinine; odds ratio, 1.965; 95% confidence interval, 1.449 to 2.664;p< 0.001), young age, male sex, high body mass index, high hemoglobin, high triglycerides, and low estimated glomerular filtration rate were significantly associated with hyperuricemia. In addition, the interactions between Pb × Cd (p= 0.010), Ni × Cu (p= 0.002), and Cr × Cd (p= 0.001) on hyperuricemia were statistically significant. Increasing levels of Pb and Cr yielded an increased prevalence of hyperuricemia, and the effect was progressively greater for increasing Cd. Moreover, increasing levels of Ni yielded an increased prevalence of hyperuricemia, and the effect was progressively greater for increasing Cu. In conclusion, our results show that high urine As is associated with hyperuricemia, and some interactions of heavy metals on hyperuricemia are noted. We also found that young age, male sex, high BMI, high hemoglobin, high triglycerides, and low eGFR were significantly associated with hyperuricemia.