Background: Body composition has emerged as a prognostic factor in cancer patients. We investigated whether sarcopenia at the diagnosis and progressive loss of skeletal muscle were associated with survival in pancreatic cancer (PC) patients receiving palliative chemotherapy. Methods: We retrospectively reviewed PC patients receiving palliative chemotherapy between 2003 and 2010. Skeletal muscle cross-sectional area at L3 was measured by computed tomography. Sarcopenia was defined using the previously published sex-specific cutoff points for Korean people. Loss of skeletal muscle was classified by sex-specific cutoffs from ROC curve. Results: Among 484 patients, 260 (53.7%) patients were more than sixty years old and 295 (61.0%) patients were male. Overall, 187 (38.6%) patients were sarcopenic at the diagnosis (male, <49.2cm²/m²; female, <31.1 cm²/m²). Decreased skeletal muscle index (SMI) during the chemotherapy, which was defined as a reduction by more than 0.21 for male and by more than 2.19 for female, was observed in 198 (77.3%) male patients and 61 (38.1%) female patients. Decreased body mass index (BMI) by more than 1 was observed in 149 patients (37.3%) without difference between genders. Median overall survival (OS) of whole patients was 8.4 months [95%CI 7.6-9.2]. In the multivariate analysis, sarcopenia (p=0.001), decreased SMI (p=0.003), and decreased BMI (p=0.001) was significantly poor prognostic factors for OS. When we analyzed four groups by SMI and BMI changes (maintained SMI and BMI, maintained SMI and decreased BMI, decreased SMI and maintained BMI, decreased SMI and BMI), the groups with maintained SMI had longer survival than the groups with decreased SMI regardless of BMI changes. Median OS was 11.5 months with maintained SMI and 8.1 months with decreased SMI (HR 0.534 and 1, p=0.004) in decreased BMI groups and 9.9 months with maintained SMI and 8.6 months with decreased SMI (HR 1 and 1.490, p=0.002) in maintained BMI groups, respectively. The analyses separately done by gender showed similar results. Conclusions: Decrease of SMI during chemotherapy was a significantly poor prognostic factor for survival regardless of BMI changes.