OBJECTIVE The study aimed to assess the accuracy and reliability of five cephalometric parameters in diagnosing class III malocclusion in Saudi and Yemeni population. METHODS A cross-sectional, descriptive study in which total 60 lateral cephalograms (30 of Saudi and 30 of Yemeni population) of Class III malocclusion were hand-traced. ANB angle, Wits appraisal, Beta angle, W angle, and Yen angle were measured. The validity, reliability, sensitivity, and positive predictive values (PPVs) of these parameters were calculated. RESULTS In Saudi population, a strong correlation was found between ANB angle and Wits appraisal (r = 0.892, P < 0.05), ANB and Beta angle showed highest sensitivity (0.933) followed by Wits appraisal (0.900), and ANB angle showed the highest PPV (0.965) followed by Beta angle (0.933) and Wits appraisal (0.931). In Yemeni population, a strong correlation was found between ANB angle and Wits appraisal (r = 0.887, P < 0.05), ANB angle and W angle showed highest sensitivity (0.966) followed by Wits appraisal (0.933), whereas W angle showed the highest PPV (1.00) followed by ANB angle (0.966) and Wits appraisal (0.933). CONCLUSIONS In Saudi population, ANB angle and Beta angle, whereas in Yemeni population, ANB angle and W angle are the most valid cephalometric indicators to accurately assess the class III malocclusion. ANB angle in the Saudi population and W angle in the Yemeni population have the highest PPV in correctly diagnosing class III malocclusion.