Background: C-reactive protein (CRP) has emerged as an important predictor for cardiovascular disease (CVD). To facilitate clinical and public health interventions, CRP thresholds have been defined as follows: low-risk (<1.0 mg/L), average-risk (1.0–3.0 mg/L), and high-risk (>3.0 mg/L). However, these cut-off thresholds are based on distributions in Western populations, and do not distinguish between men and women. Methods: We examined CRP distribution, gender difference, and determinants of CRP concentrations ranging from 0.02 mg/L to 10.0 mg/L, in 4923 Korean adults (2248 men; 2675 women) who received health checkups at Gangnam Severance Hospital from March 2006 to May 2007. Results: The distribution of CRP was highly skewed toward lower concentrations. CRP was higher in men than women, and the cut-off thresholds for the high-risk tertile of CRP concentrations corresponded to 1.01 mg/L in men and 0.62 mg/L in women, based on the current study population. Age, male gender, cigarette smoking, physical activity, body mass index, total cholesterol, high density lipoprotein cholesterol, γ-glutamyltransferase, and uric acid were independently associated with CRP concentrations. Conclusions: CRP distribution and gender difference in Korean adults were found to be different from previous Western studies, although similar risk factors influence CRP concentrations. Our results suggest that ethnicity and gender specific cut-off thresholds for CRP concentrations should be taken into consideration in CVD risk assessment. Clin Chem Lab Med 2009;47:863–9.