BACKGROUND Anti-Galalpha1-3Gal antibodies (anti-alphaGal) represent a significant fraction of natural antibodies and were implicated in several disease states, yet their origin and physiological significance remain largely undisclosed. METHODS Under a prospective observational design, we estimated anti-alphaGal immunoglobulin G (IgG)/IgM and antipig hemolytic antibody (APA) levels in 133 patients starting dialysis therapy and again after a 1-year follow-up. We used baseline data to show correlations with demographic, nutritional, inflammatory, and anemia markers and analyzed their correlation with outcomes by using univariate and multivariate strategies of survival analysis. RESULTS Serum anti-alphaGal and APA levels showed wide baseline variability, but remained relatively stable in time. Both were measurable in dialysate of peritoneal dialysis (PD) patients, showing close correlation to serum levels. We observed no association between levels of anti-alphaGal/APA and nutritional markers, but showed direct correlations of anti-alphaGal IgM (P = 0.005) and APA levels (P = 0.001) with tumor necrosis factor alpha (TNF-alpha) levels. High APA levels also were associated with severe anemia (P = 0.006). High baseline anti-alphaGal IgM (P = 0.03) and APA levels (P = 0.045) predicted later risk for enteric peritonitis in PD patients. Finally, univariate and multivariate analyses showed a consistent association between high baseline anti-alphaGal IgM (P = 0.014) and APA (P = 0.021) levels and global risk for mortality during follow-up. CONCLUSION Anti-alphaGal IgM and APA levels at the start of dialysis therapy are significant predictors of later risk for mortality and, in PD patients, enteric peritonitis. Both correlate directly with TNF-alpha levels and, in the case of APA, severity of anemia in these patients.