Patients undergoing dialysis are at high risk for cardiovascular disease (CVD). The aim of this study was to evaluate the influence of hemodialysis (HD) versus peritoneal dialysis (PD) on survival and the risk of developing de novo CVD. Of the 4191 patients with end-stage renal disease (ESRD) who started renal replacement treatment (RRT) in Lombardy between 1994 and 1997, 4064 (who were on dialysis 30 d after the start of RRT) were considered for survival analysis: 2772 were on HD (mean age 60.9 yr; 21.2% diabetic) and 1292 on PD (mean age 63.6 yr; 16% diabetic). The 3120 patients who were free of CVD at the start of RRT were included in the analysis of the risk of developing de novo CVD. HD and PD were compared by use of a Cox-regression proportional hazard model, stratified by diabetic status; the explanatory covariates were age and gender. The death rate was 13.3 per 100 patient-years (13.0 on HD and 13.9 on PD); 197 (6.3%) of the 3120 patients included in the CVD analysis developed de novo CVD (128 on HD and 69 on PD). After adjustment for age, gender, and established CVD and stratification by diabetic status, there was no significant between-treatment difference in 4-yr survival (relative risk [RR], 0.91; 95% confidence interval [CI], 0.79 to 1.06). The risk of de novo CVD did not differ significantly by treatment modality (RR, 1.06; 95% CI, 0.79 to 1.43). The risk of mortality and de novo CVD for new patients with ESRD assigned to HD or PD was similar in Lombardy in the period 1994 through 1997.