Purpose. Coagulase-negative staphylococci (CoNS) are not considered typical microorganisms causing infective endocarditis (IE). The objective was to determine variables associated with IE in patients with CoNS bacteremia. Methods. Analysis of the clinical characteristics of patients with CoNS bacteremia admitted to a university hospital in Madrid (Spain) from 2021 to December 2022 according to the occurrence of IE. Results. During the study period, 106 patients with CoNS bacteremia were detected. Twelve patients presented IE (11.3%). Echocardiogram was performed in all patients with IE and in 73 patients without IE (78.5%; p = 0.117). Of the 7 patients with heart valve prostheses, 5 patients (71.4%) had IE (p < 0.001). Patients with IE more frequently had positive blood cultures more than 12 hours after the first extraction (58.3% vs. 10.2%; p < 0.001). There was a tendency to associate community-acquired bacteremia with an increased risk of IE (p = 0.075). Attributable mortality was higher in patients with IE relative to all other patients (16.7% vs. 1.1%; p = 0.033). The multivariate analysis included having valve prosthesis and persistent bacteremia for more than 12 hours. Both were significant: valve prosthesis OR 38.6 (95% CI 5.8–258; p < 0.001) and persistent bacteremia OR 2.6 (95% CI 1.1–6.8; p = 0.046). Conclusion. A high percentage of cases of CNS bacteremia may be due to IE. Some of the variables related to a higher risk of IE, such as having a valvular prosthesis or presenting positive blood cultures for more than 12 hours, should lead us to rule out or confirm the presence of IE by performing echocardiography.