Objective: To analyze the effect of submammary fold approach and axillary approach in breast augmentation with prosthesis. Methods: 83 patients who underwent breast augmentation with prosthesis in the plastic surgery department of our hospital from January 2022 to February 2024 were selected as the study objects. The subjects were divided into axillary group (n=41) and inferior fold group (n=42) by random number table method. The lower fold group was treated with prosthesis augmentation via inferior mammary fold approach. Axillary group was treated with axillary approach prosthesis augmentation mastectomy. The operative indicators, postoperative pain degree [NRS], breast morphological changes and postoperative complication rate of the two groups were analyzed and compared. Results: There were no significant differences in the operation time of prosthesis implantation and the 3d internal drainage flow between the two groups (P>0.05). The operative time of lower fold group was significantly shorter than that of axillary group (P<0.05). The VAS scores of the two groups were not significantly different on the 1st and 2nd day after surgery (P>0.05), and the VAS scores of the lower fold group were significantly lower than those of the axillary group on the 3rd day after surgery (P<0.05). Before operation, there were no significant differences in the percutaneous distance of the papilla-submammary fold, sternal incisor-nipple distance, papilla-median line distance and total breast volume between the two groups (P>0.05). After operation, the linear distance and total breast volume of both groups were significantly higher than those before operation (P<0.05). However, there were no significant differences in postoperative linear distance and total breast volume between the two groups (P>0.05). The incidence of postoperative complications was not significantly different between the two groups (P>0.05). Conclusion: The submammary fold approach or axillary approach is used in breast augmentation with prosthesis. The implantation time, postoperative drainage volume and postoperative complication rate are similar, and ideal breast morphology can be obtained in all cases. However, compared with the axillary approach, the operation time of the submammary fold approach is shorter, and the postoperative pain is less.