Introduction Although pancreatic cancer ranks seventh in cancer-related deaths, it is an extremely fatal disease, and more than 330,000 people die from this disease worldwide. Although there are many first-line treatment studies in the literature, there are almost no prospective studies regarding second-line therapy. Therefore, there is no standard approach in the second-line treatment of pancreatic cancer. We decided to conduct this study to investigate second-line treatments with problems such as cost, treatment efficacy, and toxicity. Methods Patients older than 18 years old who applied to Ege University Hospital medical oncology department with a diagnosis of metastatic pancreatic cancer, who received first-line chemotherapy due to their illness, and who had progressed afterwards were included in the study. The files of the patients who applied between 2013 and 2017 were examined. Results Our study's primary endpoint was progression-free survival, and it was found that the median progression-free survival was 3.2 months in the Xelox patients, 3.7 months in the gemcitabine-nab paclitaxel patients, and 3.5 months in the other regimens. When the secondary endpoint was evaluated, overall survival, the median overall survival was 5.9 months in the Xelox patients, 5.3 months in the gemcitabine-nab paclitaxel patients, and 4.8 months in the other regimens. Conclusion As a result, second-line treatments were compared, and no statistically significant difference was found between them. For this reason, the side effects of previously used drugs and the side effects of new drugs to be used, as well as their costs, should be evaluated when choosing a treatment.