Background and Objectives: Catheter-related bloodstream infections (CRBSI) and infective endocarditis (IE) lead to substantial morbidity, prolonged hospitalizations, and increased mortality. This study aimed to determine the incidence of IE among hospitalized HD patients with CRBSI and identify risk factors associated with 90-day all-cause mortality. Materials and Methods: We conducted a retrospective analysis of patients diagnosed with CRBSI. Clinical, microbiological, and echocardiographic data were evaluated. Risk factors for 90-day mortality were analyzed using univariate analysis and multivariable Cox proportional hazards regression models. Results: A total of 130 patients were included. Gram-positive organisms were the predominant pathogens (59.6%), with Staphylococcus aureus identified in 27.5% (n=30) of cases. Gram-negative bacteria accounted for 21.1% of infections. IE was diagnosed in 17 patients, representing an incidence of 13.1% within the CRBSI cohort. Significant differences were observed between the IE and non-IE groups regarding the need for surgery, hemoglobin levels, length of hospital stay, and microbial etiology (p < 0.05). The 90-day all-cause mortality rate was 10.8% (n=14). Univariate analysis identified older age, female gender, history of heart failure, and hypoalbuminemia as factors associated with increased mortality (p < 0.05). In the multivariable Cox regression, age remained the sole independent predictor of 90-day mortality (Hazard Ratio: 1.047; 95% CI: 1.0–1.096; p=0.048). Conclusions: Staphylococcus aureus is the leading pathogen in HD patients with CRBSI and IE. Given the 13.1% IE incidence, routine echocardiographic screening represents a clinically sound and justified strategy for patients with CRBSI, regardless of initial culture results, to ensure early diagnosis and intervention.