Background: Apatinib has been proved to be effective and well tolerated among patients in phase II and III studies. Here, we evaluated the safety and effectiveness of apatinib in advanced gastric cancer patients in a real-world setting. Methods: This study enrolled advanced gastric cancer patients who had progressed or relapsed despite systemic chemotherapy. The primary outcome was safety and the secondary outcomes included overall survival (OS) and progression-free survival (PFS). Results: A total of 337 patients were included. In total, 62 (18.4%), 102 (30.3%), and 173 (51.3%) patients received first, second, and third or higher line apatinib therapy, respectively. Grade 3/4 treatment-emergent adverse events (AEs) were infrequent (<5%), with hypertension (6.8%) being the only grade 3/4 AE occurring in more than 5% of the patients and across the low-dose (250 mg, 7.3%), mid-dose (425–500 mg, 6.1%), and high-dose group (675–850 mg, 2/15, 13.3%). The median OS and PFS were 7.13 months (95% CI, 6.17–7.93) and 4.20 months (95% CI, 4.60–4.77), respectively, and were comparable among the low-, mid-, and high-dose groups. Conclusion: Lower daily doses of apatinib achieved comparable OS and PFS versus higher daily doses of apatinib while maintaining a more benign safety profile in advanced gastric cancer patients. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT02668380. © The Author(s), 2020.