Objective: Pancreatic cancer is one of the leading causes of cancer-related death. Despite the introduction of new therapeutic agents, survival rates remain low. Furthermore, few trials have evaluated the options for second-line therapy and the prognostic variables. In this study, we aimed to determine the real-world efficacy and prognostic parameters of second-line treatment for advanced pancreatic cancer. Material and Methods: Patients with advanced pancreatic cancer from different centers who received second-line treatment were enrolled in the study. The patients’ demographic, clinical, and pathological characteristics were retrieved retrospectively. Results: A total of 161 patients were enrolled in the study. The majority of the patients (50.3%) received oxaliplatin plus fluoropyrimidine as second-line treatment. The median progression-free survival and overall survival for the entire cohort were 2.5 months and 4.5 months, respectively. In univariate analyses, an Eastern Cooperative Oncology Group performance status ≥2, age ≥65 years, hypoalbuminemia, thrombocytosis, presence of metastatic peritoneal disease, elevated alkaline phosphatase and carcinoembryonic antigen levels, and a neutrophil-lymphocyte ratio (NLR) ≥3 were identified as poor prognostic factors. In multivariable analyses, low albumin level (p=0.031) and high NLR (p=0.05) were found to be independent prognostic factors for overall survival. Conclusion: Pancreatic cancer is a unique malignancy, and advanced disease has a dismal prognosis. In univariate analyses, we identified multiple factors that were poor prognostic variables. In particular, the albumin level and NLR were independent prognostic factors for overall survival, and these parameters might be useful in selecting the second-line treatment and predicting the survival of these patients.