This prospective observational study had two aims: (I) to assess whether a preoperative dental screening before endoprosthesis (EP) implantation with need-based dental intervention would decrease the prevalence of periprosthetic joint infection (PJI) and (II) to evaluate whether instructed orthopedic surgeons would achieve similar results in oral screening as dentists. The preoperative oral health statuses of the patients, prior to EP insertion, were either evaluated by the patients’ general dentists (Ia) or, if the patient had not visited a general dentist, by an instructed orthopedic surgeon (Ib). Both the dentist and orthopedic surgeon used standardized risk estimation (low risk, moderate risk, and high risk) for an oral-health-related infectious complication after EP insertion, including a recommendation for further management of the patient. If required, a need-based dental rehabilitation was performed. In addition, retrospective data evaluation of a comparison group (II) was performed, which had not been screened orally preoperatively. A total of 777 patients (screening group (I):n= 402, of which 229 were screened by a dentist (Ia), 173 were screened by an orthopedic surgeon (Ib); comparison group (II):n= 375) were included. No general association between early infection rate and preoperative oral screening in general was found (1% PJI in screening group (I), 1.6% PJI in comparison group (II);p= 0.455). However, screening performance (dentist vs. orthopedic surgeon) had a significant impact on the prevalence of developed PJIs (p= 0.021). Thereby, 100% of observed infections in the screening group (I) occurred in the group with previous oral screening by an orthopedic surgeon (Ib). Furthermore, the C-reactive protein (CRP) value at discharge was significantly lower when general preoperative oral screening had been performed (group I vs. group II,p= 0.03). Only preoperative oral screening by a dentist had the potential to reduce oral-focus-associated EP infections; therefore, increased attention should be paid to the further promotion of interdisciplinary work between dentists and orthopedic surgeons. Dental screenings, using objectifiable criteria, as applied in this study, seem reasonable but require further validation in larger cohorts.