Background: Available information on endodontic treatment outcome derives from clinical studies, of which the main part is observational with no randomization and little or no control of confounding factors. Several sources of bias may hamper the interpretation of results from observational studies if the problems are not addressed properly. Objective: The purpose of this narrative review is to describe and explain the potential benefits of employing epidemiological methodology when designing, conducting and reporting on observational, clinical outcome studies. Discussion: Epidemiology provides methodology that can be used to reduce the impact of several types of problems related to observational studies. These problems concern, external validity, which describes the generalisability of the study findings, and internal validity, which describe data quality parameters, such as selection bias, information bias and confounding. Furthermore reporting of a study should be systematized, and to that use, several checklists have been developed. Conclusion: It can be concluded that epidemiological methods are important for conducting and interpretation of findings from clinical, observational studies in endodontology.