Background: Reduction mammoplasty effectively improves quality of life for women with macromastia. However, little is known whether surgical- or patient-related factors affect satisfaction. Objective: The authors sought to investigate factors associated with altered patient satisfaction following reduction mammoplasty. Methods: A cross-section study was performed by sending the BREAST-Q Reduction module to all patients who had undergone reduction mammoplasty between January 2009 and December 2018 at 2 tertiary Danish hospitals. Demographics and pre-, peri-, and postoperative details were gathered from electronic medical records. Results: A total of 393 patients returned the questionnaire and were eligible for the study. Increasing age at the time of surgery was associated with higher satisfaction with breasts nipples, headache, psychosocial well-being, and outcome. Increased body mass index at the time of surgery negatively affected satisfaction with breasts and psychosocial well-being. Increase in body mass index after surgery was further associated with lower satisfaction with breasts, nipples, sexual well-being, and more pain in the breast area. Postoperative scar revision and wound infection was more common following inferior pedicle technique than superomedial technique and negatively affected satisfaction with outcome and pain in the breast area. Conclusions: Patients should be motivated to optimize their weight prior to reduction mammoplasty to achieve optimal satisfaction. Age was associated with improved patient satisfaction, which should considered when operating on younger patients. Postoperative complications affect patient satisfaction, and the superomedial technique seems to be a better choice than the inferior pedicle technique in medium-large breasts.