A phase II study was designed to evaluate the efficacy and safety of oxaliplatin as second-line treatment in patients with locally advanced or metastatic pancreatic cancer. Eighteen patients with advanced pancreatic cancer previously treated with gemcitabine-based chemotherapy, received oxaliplatin 130 mg/m2 i.v. every 21 days. Patients were treated until tumor progression or unacceptable toxicity. No objective response was observed among the 18 treated patients. Three (16.7%) patients had stable disease for > 2 months. A clinical benefit response was observed in five (27.7%) patients. Toxicity was mild. Oxaliplatin as second-line treatment for patients with unresectable pancreatic cancer is well tolerated and associated with improvement of tumor-related symptoms despite its failure to induce objective responses. LOHP merits further investigation in combination with other drugs as palliative treatment of pretreated patients with advanced pancreatic cancer.