Serum uric acid (UA) is the final product of purine metabolism in humans. The present study is aimed at identifying the potential association between serum UA and early-onset coronary artery disease (EOCAD). The study population consisted of 1093 EOCAD patients aged ≤50 years, and 1117 age- and sex-matched apparently healthy people served as controls. The concentrations of UA were measured by uricase method. The severity of CAD was evaluated by Gensini score. The mean serum level of UA was 5.843 ± 1.479 mg/dl in EOCAD patients and 5.433 ± 1.529 mg/dl in controls. Serum UA levels were significantly higher in the EOCAD group than those in the control group (P < 0.001) and was an independent risk factor for EOCAD (OR = 1.100, 95% CI: 1.022-1.185). The early-onset myocardial infarction patients with 3-vessel disease had higher serum UA levels than those with 1- or 2-vessel disease. The serum UA levels of EOCAD patients with acute coronary syndrome were significantly higher than those with chronic coronary artery disease. EOCAD patients with hyperuricemia had higher Gensini scores than those without hyperuricemia. In addition, the serum UA levels were affected by drinking (P < 0.01) and were positively correlated with serum creatinine (r = 0.323) and weight (r = 0.327). Our results show that serum UA was an independent risk factor for EOCAD. The serum UA levels were associated with the presence and severity of EOCAD and suggested that UA may be involved in the progression of EOCAD.