Background/Aims: The efficacy and tolerability of oxaliplatin in combination with either folinic acid, fluorouracil (5-FU) (FOLFOX4 regimen) or capecitabine (XELOX regimen) was evaluated in advanced pancreatic cancer. Methodology: In this study, eighty-five patients with advanced pancreatic cancer were enrolled after failing to gemcitabine-based chemotherapy between November 2005 and August 2011. FOLFOX4 was repeated every two weeks and XELOX regimen was repeated every three weeks until either disease progression or unacceptable toxicity occurred. Results: Eighty-five patients were evaluated for tumor response. Seven patients (18%) achieved a partial response with XELOX and stable disease was observed in 16 patients (41%). Eight patients (17%) achieved a partial response with FOLFOX4 and stable disease was observed in 12 patients (26%). Disease control rates were 59% in the XELOX arm and 43% in the FOLFOX4 arm. The median time to progression was 16 weeks in both arms. The median overall survival was 21 weeks with XELOX and 25 weeks with FOLFOX4. Conclusions: Oxaliplatin-based combination therapy showed moderate clinical activity with acceptable toxicity in patients who had progressive disease after receiving gemcitabine-based chemotherapy for advanced and/or metastatic pancreatic cancer. We conclude that XELOX is similar in terms of efficacy and toxicity profile to FOLFOX4 in the second-line treatment of metastatic pancreatic cancer.