Endodontic-periodontal diseases frequently pose significant challenges for clinicians in terms of diagnosis, management, and prognosis. Practitioners' knowledge of endo-periodontal lesion (EPL) diagnosis is essential for formulating appropriate treatment plans. This study aimed to evaluate the knowledge of diagnostic and therapeutic approaches to EPLs among dental practitioners in Saudi Arabia. The study used a cross-sectional survey among Saudi Arabian dental practitioners using a self-administered questionnaire. The statistical methods used included descriptive analysis, Pearson's chi-square test, Fisher's exact test, and binary logistic regression. Results: The study included 312 respondents, with 95 (30.4%) females and 217 (69.6%) males. The majority were aged 25 to 30 (n = 155, 49.7%). Significant associations were found between participant knowledge and the following variables: age (P < 0.001), organization (P = 0.005), employment (P = 0.001), professional experience (P < 0.001), postgraduate degree (P = 0.002), specialty (P < 0.001), Saudi Commission for Health Specialities (SCHS) rank (P = 0.004), and continuing training (P = 0.043). Additionally, individuals aged 36-40 were 4.3 times more likely to have good knowledge compared to those aged 25-30 (adjusted odds ratio [AOR] = 4.27, P = 0.020), and lecturers were 4.4 times more likely to have good knowledge compared to interns (AOR = 4.40, P = 0.054). This indicates that the practitioners' overall knowledge was above average and that they possess a fundamental understanding of EPLs. These findings have valuable effects on clinical practice, suggesting that evidence-based guidelines and targeted educational programs can enhance the practitioners' diagnostic accuracy and treatment strategies for EPLs, ultimately improving patient outcomes and clinical efficacy.
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