Introduction: Reduction mammoplasty alleviates physical and psychological discomfort in patients with large breasts. The present study sought to determine preoperative markers that may herald postoperative complications. Methods: The NSQIP 2021 data file was queried using CPT and ICD-10 diagnosis codes to identify patients who underwent reduction mammoplasty at participating hospitals. To reduce confounders, patients undergoing gender affirming surgeries and males were excluded from the analysis. Preoperative comorbidities and laboratory values were analyzed using univariate and multivariate regression to determine their association with overall 30-day postoperative complications. Results: In total, 5909 reduction mammoplasty patients were identified. Patients aged ≥ 65 years had 1.47 times higher odds of developing complications after breast reduction compared to those who were younger in age (95% CI 1.02 – 2.07, P < 0.05). Tobacco use had 1.65 times higher chance of developing complications after their surgery compared to no tobacco use (95% CI 1.11-2.38, P < 0.05) and similarly, patients with ASA class III-V had 1.6 times higher odds of complications after their surgery compared to ASA class I-II (1.25-2.03, P < 0.05). Conclusion: Patients aged ≥ 65 years, those who smoke tobacco, have obesity (BMI ≥ 30), and/or are classified as ASA III–V are significantly associated with increased 30-day complication rates following reduction mammoplasty. Preoperative counseling of these patients should emphasize the importance of modifying risk factors—such as smoking cessation and weight reduction—and clearly communicate their high risk of postoperative complications to support informed decision-making and foster realistic patients expectations.