Aim To investigate the relationship between Helicobacter pylori (Hp) infection and plasma lipoprotein-associated phospholipase A₂ (Lp-PLA₂) levels, carotid atherosclerosis (CAS) in patients with chronic renal failure (CRF). Methods According to the results of ¹⁴C urea breath test, 200 patients with chronic renal failure were divided into two groups:CRF complicated with Hp infection group (CRF-Hp group, n＝119) and CRF not complicated with Hp infection group (CRF-nHp group, n＝81). According to the degree of CAS, CRF-Hp group was divided into 3 subgroups:carotid intima-media thickness (CIMT) thickening group, stable plaque group and unstable plaque group. The level of plasma Lp-PLA₂ was detected by enzyme-linked immunosorbent assay (ELISA) method. CIMT and atherosclerotic plaques were measured by high resolution two dimensional ultrasound technique. The relationships between Hp infection and plasma Lp-PLA₂ levels, CIMT and plaque stability were analyzed in CRF patients. Results The plasma Lp-PLA₂ level and CIMT in CRF-Hp group were higher than those in CRF-nHp group (P＜0.01). There was significant difference in the composition of CAS type of CRF-Hp group and CRF-nHp group (χ²＝15.637, P＝0.0004). In the 3 subgroups of the CRF-Hp group, there was significant difference in plasma Lp-PLA₂ level in the unstable plaque group, stable plaque group and CIMT thickening group (P＜0.01). Pearson correlation analysis showed that plasma Lp-PLA₂ level was positively correlated with CIMT in CRF-Hp group (r＝0.649, P＜0.01). Conclusion Hp infection is likely to promote the occurrence and development of CAS through influencing Lp-PLA₂ metabolism and increasing CIMT and instability of CAS plaque in CRF patients.