Background: We designed a single-arm, open label phase II study to determine the efficacy and toxicity of the combination of pazopanib with CapeOx (capecitabine and oxaliplatin) in metastatic and/or recurrent advanced gastric cancer (AGC) patients. Methods: Previously untreated AGC patients received capecitabine (850 mg/m² bid, day 1–14) plus oxaliplatin (130 mg/m², day 1) in combination with pazopanib (800 mg, day 1–21) every three weeks. Treatment was continued until progression of the disease or intolerable toxicity was observed. Results: In all, 66 patients were treated with pazopanib plus CapeOx. The median age of the patients was 51.5 years (range, 23.0–77.0 years), and the median ECOG performance status was 1 (0–1). Among all 66 patients, one complete response and 37 partial responses were observed (overall response rate, 57.6%; 95% confidence interval (CI), 46.7–67.9%). Stable disease was observed in 22 patients (33.3%), revealing a 90.9% disease control rate. The median progression free survival and overall survival were 6.5 months (95% CI, 5.6–7.4 months) and 10.5 months (95% CI, 8.1–12.9 months), respectively. Thirty-four patients (51.5%) experienced a treatment-related toxicity of grade 3 or more during the study. The most common toxicities of grade 3 or more were neutropenia (15.1% of all patients), anemia (10.6%), thrombocytopenia (10.6%), anorexia (7.6%), nausea (3.0%), and vomiting (3.0%). There were no treatment-related deaths. Conclusions: The combination of pazopanib and CapeOx showed moderate activity and an acceptible toxicity profile as a first-line treatment in metastatic and/or recurrent AGC patients(ClinicalTrials.gov NCT01130805). Clinical trial information: NCT01130805