Purpose: To identify a subgroup at high risk for loco-regional recurrence (LRR) from T1-2 breast cancer with negative lymph nodes (N0) after mastectomy by using a meta-analysis. Methods and materials: Published studies on the relationship between clinical features and LRR of breast cancer were identified from public databases, including PubMed, EMBASE, and the Cochrane Library. High-risk features for LRR in this patient population were defined based on the pooled results of meta-analysis. Results: For the meta-analysis, a total of 11244 breast cancers with pT1-2N0 after mastectomy from 20 publications were included for analysis. The pooled results indicated that age (hazard ratio (HR) 1.77, P =0.001), lymphovascular invasion (LVI) (HR 2.23, P <0.001), histologic grade (HR 1.66, P <0.001), HER2 status (HR 1.65, P =0.027), menopausal status (HR 1.36, P =0.015), and surgical margins (HR 2.56, P =0.014) were associated with a significantly increased risk of developing LRR in this patient population group, but not for tumor size (HR 1.32, P =0.23), systematic therapy (HR 1.67, P =0.20), and hormonal receptor status (HR 1.04, P =0.73). Conclusion: In the current study, patients with young age, positive LVI, high histologic grade, HER-2 positive, premenopausal, and positive surgical margins have an increased risk of developing LRR. Further prospective trials are needed to clearly define the role of adjuvant postmastectomy radiotherapy in T1-2N0 breast cancer at high risk of developing LRR.