Background: Erlotinib is the only targeted agent in combination with gemcitabine showing significantly improved outcomes in pancreatic cancer. Although combining platinum agent with gemcitabine has not provided clear survival benefit over gemcitabine alone, gemcitabine plus platinum resulted in improved response rate and progression-free survival (PFS). We tried to evaluate whether the addition of oxaliplatin to gemcitabine/erlotinib confers a clinical benefit to patients with locally advanced or metastatic pancreatic cancer. Methods: Chemotherapy-naïve patients with locally advanced or metastatic pancreatic cancer were randomly assigned to receive GEMOX-T (gemcitabine 1000mg/m² IV and oxaliplatin 50mg/m² IV on day 1, 8 plus erlotinib 100mg daily, every 3weeks) or GT (gemcitabine 1000mg/m² IV on day 1, 8 plus erlotinib 100mg daily, every 3weeks). The primary endpoint was overall response and secondary endpoints included PFS, overall survival (OS) and toxicity. Results: Between May 2013 and April 2016, 65 patients were randomly assigned to treatment group (33 in GEMOX-T arm, 32 in GT arm). The median age of all patients was 61 years (range, 41-76) and about 80% of patients had metastatic disease. The overall response rate was 18.2 % in GEMOX-T arm and 6.2% in GT arm (P = 0.051). The disease control rate was significantly superior in GEMOX-T arm compared to GT arm (72.7% vs. 43.8%, P = 0.019), with 1 patient in GEMOX-T group continuing the treatment with stable disease. After a median follow up of 19.7 months, there was significant difference in PFS: the median PFS were 3.9 months for GEMOX-T arm and 1.4 months for GT arm (Hazard ratio: 0.58, 95% CI 0.35-0.96, P = 0.037). However, it did not translate to improvement of OS (median OS; 6.2 m for GEMOX-T arm, 5.1 m for GT arm, P = 0.118). The most common grade ≥ 3 hematologic adverse events were neutropenia (16.9%) and anemia (13.8%). Conclusions: The addition of oxaliplatin to 1^st line gemcitabine/erlotinib regimen demonstrated higher response rate and significantly improved PFS in patients with locally advanced or metastatic pancreatic cancer.