The aim of this study was to analyze the antibiotics prescription habits, both prophylactically and therapeutically, of Spanish general dental practitioners in the management of endodontic infections in primary care. Two hundred Spanish general dental practitioners were asked to respond to a survey on indications for antibiotics prescription in the treatment of endodontic infections, being 190 general dentists (95%) included in the study. Data were analyzed using descriptive statistics and the chi-square test. The average duration of antibiotics therapy was 6.5 ± 1.0 days. In patients without medical allergies, most of them (97%) selected amoxicillin as the antibiotic of the first choice, alone (51.1%) or associated with clavulanic acid (45.8%); in patients with penicillin allergies, the drug of choice was clindamycin 300 mg (70%). For cases of symptomatic irreversible pulpitis, 44% of the respondents prescribed antibiotics, in the scenario of prophylactic antibiotic prescription, up to 27% of the general dentists prescribe according to non-current guidelines (1 g 1 h before or 1 g 1 h before and 1 g 1 h after) in non-indicated cases (16% in patients taking oral bisphosphonates). It is necessary to improve the antibiotic prescription habits of Spanish general dentists in endodontics.