Intermaxillary tooth size discrepancy (TSD) is the disproportion in patients’ tooth size that is usually referred to the Bolton analysis. This size imbalance may also affect the outcome of orthodontic treatment. Therefore, this retrospective study was conducted to determine the prevalence of intermaxillary tooth size discrepancy (TSD) beyond 2 standard deviation (2 SD) from Bolton’s mean in orthodontic patients and to evaluate the effect of TSD beyond 2 SD of Bolton’s mean on orthodontic treatment outcomes. A total of 226 sets of orthodontic study models that met the selection criteria were selected from 3077 orthodontic cases. Bolton's analysis of the anterior and overall ratios was performed on each of the pre-treatment models. The orthodontic treatment outcomes for the cases which were identified of having TSD beyond 2 SD were evaluated and any interventional techniques to improve the outcome of the treatment were recorded. The results showed that 29.20% of cases had TSD beyond 2 SD of Bolton’s mean. 26.54% of cases had anterior ratio of more than 2 SD. Meanwhile, 7.08% of cases had an overall ratio greater than 2 SD. Of all cases with TSD beyond 2 SP, most of these cases (62.12%) had affected the outcome of orthodontic treatment. In conclusion, there is more than one quarter of orthodontic patients present with TSD beyond 2 SD of Bolton’s mean which may influence the outcome of orthodontic treatment. Intervention techniques should be carefully planned to achieve satisfactory treatment outcomes.