Background: Lapatinib is approved for the treatment of metastatic HER2-overexpressed breast cancer with capecitabine after progress on anthracycline, taxane, and trastuzumab in China. A post-marketing pharmacovigilance program was carried out to verify the real-world safety and the efficacy information of lapatinib. Methods: This was a prospective, non-interventional, long-term study in the real-world setting. All patients treated with lapatinib during the program (inclusion period 12 months) in Fudan University Shanghai Cancer Center (FUSCC) were included. The main outcome measures were progression-free survival (PFS) and incidence of adverse events. Results: A total of 112 patients were enrolled. The median age was 52 years, 64.3% of patients were postmenopausal, 90 patients (80.4%) had stage IV disease, and the most common metastatic site was in the lung (43.8%), bone (30.4%), liver (26.8%), and brain (18.8%). About half of the patients (46.4%) experienced 3 or more systemic regimens before lapatinib. After a median follow-up of 34.3 months (range, 17.9-57.9 months), the median PFS was 8.1 months (95% CI, 5.8 to 10.4 months). Later phase of disease (stage IV), 3 or more prior treatments, pulmonary metastasis, liver metastasis, prior anthracycline or taxane, and poor adherence strongly correlated with worse survival (P<0.005). The grade 3 or 4 adverse events were diarrhea (9.8%), hand-foot syndrome (5.4%), and rash (4.5%). Conclusions: Upon implementation of lapatinib therapy in a real-world setting, the case mix was characterized by more early-stage breast cancer patients. The median PFS was slightly superior to what was published in the clinical trials. Pulmonary metastasis or liver metastasis significantly correlated with worse survival. We reported a similar prevalence of adverse events.