The α-chain alleles 1 and 2 of haptoglobin (Hp) molecule account for three phenotypes, which have biologically important differences in their antioxidant, scavenging, and immunomodulatory properties and may thereby influence the course of inflammatory diseases. A follow-up observational study was conducted to assess the association between haptoglobin phenotype and the development of clinically significant bacterial infections in patients with liver cirrhosis. Sera of 336 patients with liver cirrhosis of various etiologies and 384 healthy subjects were investigated. Haptoglobin phenotypes were determined by gel electrophoresis and assigned corresponding genotype. Haptoglobin phenotype distributions of patients and controls was similar (Hp1-1: 10.7% vs 11.5%, Hp2-1: 47.9% vs 46.1% and Hp2-2: 41.4% vs 42.4%). The probability of clinically significant bacterial infections was calculated for each haptoglobin phenotype (Hp1-1: 50.0%, Hp2-1: 36.0% and Hp2-2: 26.6%, p = 0.039). In a logistic regression analysis, Hp1-1 phenotype (p = 0.015, OR: 2.74, 95% CI: 1.22-6.13), Child-Pugh stage (p = 0.038, OR: 1.40, 95% CI: 1.02-1.91) and presence of co-morbidities (p < 0.001, OR: 2.64, 95% CI: 1.63-4.27) were independently associated with infections. In a Cox regression analysis, Hp1-1 phenotype (p = 0.014), Child-Pugh stage C (p < 0.001), and presence of co-morbidities (p = 0.004) were associated with time to first infectious episode. Phenotypic haptoglobin polymorphism was independent predictor for risk and time to first clinically significant bacterial infectious episode.