Objective:To evaluate the applicability of Moyers and Tanaka-Johnston mixed dentition prediction methods among patients attending dental outpatient departments in tertiary care hospitals in rural Sindh, Pakistan. Methods:A cross-sectional study was conducted over six months, involving 300 patients (150 males and 150 females) aged 8-12 years from Bhitai Dental and Medical College, Mirpurkhas. Patients selected had all sound erupted permanent teeth except second and third molars, with no history of orthodontic treatment. Mesiodistal widths of teeth were measured using Mitutoyo digimatic calipers. Data was analyzed using SPSS-16, employing Student’s t-test, paired t-tests, and simple linear regression to derive new prediction equations. Results:Significant discrepancies were found between the predicted and actual widths of unerupted canines and premolars using Moyers and Tanaka-Johnston methods, indicating these methods are unsuitable for this population. New regression equations were derived for the local demographic. Conclusion:The Moyers and Tanaka-Johnston prediction methods are ineffective for the population in rural Sindh. The study recommends the development of localized prediction models and further multicenter studies with larger, diverse samples to refine these equations. These findings are crucial for accurate orthodontic treatment planning and improving patient outcomes.