Background. To establish the baseline cutoff value of C-reactive protein (CRP) that would predict increased overall and cardiovascular mortality in patients with end-stage renal disease (ESRD). Methods. A cohort of 270 prevalent hemodialysis patients treated at Rijeka University Hospital was eligible for the study. Monthly CRP measurements were performed for three consecutive months. Only the patients with CRP values varying <20% were included (n=256). During the follow-up, 24 patients were transplanted and therefore excluded from the analysis. The CRP cutoff point of 6.2 mg/L was established by Receiver Operating Characteristic curve. The patients were divided into four groups according to their CRP values. Group 1 included 80 (34.5%) patients with CRP <3.0 mg/L, group 2 included 23 (9.9%) patients with CRP 3.0–6.1 mg/L, group 3 consisted of 18 (7.7%) patients with CRP 6.2–10.0 mg/L, and group 4 included 111 (47.9%) patients with CRP >10.0 mg/L. The survival was evaluated by Kaplan-Meier curve. Results. During the two-year follow-up, 59 patients died. The major cause of death was cardiovascular disease (64%). Significantly higher overall and cardiovascular mortality was observed in group 3 when compared with groups 1 and 2 (χ2=11.97; P < 0.001) and in group 4 when compared with groups 1 and 2 (χ2=14.40; P<0.001). Compared with survivors, non-survivors had a higher median CRP value (19.0 [1.5–99.7] mg/L vs. 2.3 [0.1–49.1] mg/L, respectively; P<0.001). Conclusion. Serum concentration of CRP above 6.2 mg/L is a strong predictor of overall and cardiovascular mortality in patients with ESRD.