Background: A pharmacoeconomic analysis of the RISCAVID database aimed at assessing the cost effectiveness of phosphate binders in preventing CV mortality and morbidity over 7 years was performed. Methods: Morbid or fatal events occurring in 750 chronic HD patients were recorded. Statistical analysis evaluated the distribution of variables and the effect of sevelamer on survival. A cost-effectiveness evaluation was performed using a probabilistic model based on a Markov chain. Results: Multivariate analysis showed that treatment with sevelamer was associated with a reduced stroke incidence by 52% (p = 0.04) and reduced levels of C-reactive protein (p < 0.01). Cost-effectiveness evaluation evidenced a 33% decrease in hospital-days for patients treated with sevelamer, with and without comorbidities compared to patients undergoing calcium binders treatment. Conclusion: Treatment withsevelamer was associated with a reduced risk of stroke in HD patients, with a clear saving on disease-related costs for the Italian National Healthcare System.