This study aimed to develop a straightforward and accurate index of impacted third molar removal difficulty through analyzing various factors to assess the difficulty level of impacted mandibular third molar (IMTM) extraction. This prospective cohort study included 203 patients who required IMTM extraction. All patients were selected using the preset selection criteria. The present study assessed operation difficulty with operating time. A mathematical model and regression analysis were performed to explore 6 main factors (age, number of roots, degree of bone impaction, shape of roots, and impaction angle and its relation). Appropriate correction coefficients were obtained to formulate a new IMTM removal difficulty predictive index. Consistency of the κ value was checked to evaluate performance. Degree of bone impaction had the highest correlation coefficient (0.576), followed by shape of roots (0.359), and the lowest correlation coefficient was for number of roots. The Pederson index for these 203 patients showed that 75, 76, and 52 patients had low, moderate, and high difficulty levels, respectively, whereas the new index categorized 78, 85, and 40 patients as having low, moderate, and high difficulty. Comparison of the Pederson index and new index with operating time showed κ agreements of 65.30 and 77.9% (P<.01), suggesting that the prediction results of the new index are more objective and accurate. The newly proposed index is straightforward and efficient and exhibited promising results in κ agreement. Because of its straightforward nature, it is better suited for Chinese public hospitals with a large volume of patients who require alveolar surgery. The detection of predictor variables could be useful for graduate students, professionals, and general dental practitioners contemplating IMTM removal to assess the difficulty level of IMTM extraction.