Plastic surgeons aim to achieve symmetry in breast surgeries, which is the main determinant of chest aesthetics. The aim of this study was to verify if preoperative breast asymmetry is a predictor of postoperative asymmetry in women undergoing breast reduction. In this prospective study, we enrolled 71 women (the mean age 37 years, SD 10 years) with breast hypertrophy who underwent reduction mammaplasty. We collected clinical data including age, height, weight, weight of the resected tissues, and performed pre and postoperative photographic documentation. The following measurements of both breasts were analyzed: volumes (vol), nipple–sternal notch distance (A-sn), difference between nipples’ levels (A-A’), nipple–midline distance (A-ml), difference between inframammary folds levels (IF-IF’), distance between inframammary fold and nipple (IF-A), distance between inframammary fold apex and midline (IF-ml). All measurements were performed preoperatively and 6 months after the surgery and asymmetries of all variables were calculated (asy-vol, A-A’, asyA-sn, asyA-ml, IF-IF’, asyIF-A, asyIF-ml). Postoperative asymmetry of breast volumes and nipples position was not associated with any of the analyzed clinical variables. Postoperative asymmetry of nipples’ level was associated with preoperative asymmetry of IF-ml; however, logistic regression did not detect any preoperative measurement influencing postoperative volume and nipples’ level asymmetry. Moreover, we found that preoperative asyIF-ml increased the risk of postoperative volume asymmetry, which is above the average (52 cc) (OR = 2.04). Postoperative breast asymmetry after breast reduction is not related neither to preoperative asymmetries nor clinical variables; however, asymmetry of inframammary fold apex to the midline may be the factor affecting postoperative volumetric asymmetry.