Background: Pancreatic cancer median age at diagnosis is 70 years old. However, elderly pts are underrepresented in randomized clinical trials (RCTs) and chemotherapy efficacy and safety data in this population are limited. Herein, we present a retrospective analysis of an elderly population treated at our Institution, investigating the role of baseline clinical factors in guiding treatment decision making. Methods: Pts aged ≥70 years old receiving a first-line chemotherapy for APC were included in the analysis. The primary end-points were progression-free survival (PFS) and overall survival (OS). The following variables were collected: gender; age (≥ 70 and < 75 years vs ≥ 75 years); baseline ECOG PS (0-1 vs 2-3); site of primary tumor (head/uncinate process vs body/tail); disease stage (locally advanced vs metastatic); baseline CA 19.9 ( < vs ≥ 200); chemotherapy regimen; comorbidities (yes vs no); number of comorbidities (0-1 vs ≥ 2). Univariate and multivariate analysis for PFS and OS were performed. Results: A total of 169 APC pts aged ≥70 years old, receiving first-line chemotherapy between March 2015 and August 2020, were included in the analysis. The median age was 76 years (70-89), ECOG PS was 0-1 in 77% of pts; 70% were metastatic; 70% of pts had a head/uncinate process primary tumor; 25% had baseline CA 19.9 ≥ 200; 9.4% of pts had no comorbidities and 50% had ≥2 comorbidities. The majority of pts received gemcitabine nab-paclitaxel (60%), other regimes included gemcitabine (28%), FOLFIRINOX (5%), capecitabine (4%), FOLFOX (2%) and FOLFIRI (1%). The overall population median PFS and OS were 6.5 (median follow-up 19.1 months) and 11 months (median follow-up 21.8 months), respectively. Out of 164 pts evaluable, 38 (23%) pts achieved a partial response and 58 (35%) a stable disease, with a disease control rate of 58%. At the multivariate analysis, ECOG PS 0-1 resulted independently associated both with improved PFS (p 0.005) and OS (p 0.0084). At the multivariate analysis for PFS, also locally advanced stage resulted significantly associated with better PFS (p = 0.036). In pts with ECOG PS 0-1 vs 3-4 the median PFS was 6.7 vs 3.3 months (p 0.0004) and median OS was 11.3 vs 5.5 moths (p 0.003), respectively. Conclusions: Despite the retrospective nature of the analysis and the limited sample size, we observed that elderly APC pts can benefit from a first-line treatment achieving survival outcomes comparable to the one reported for younger pts in RCTs. On the basis of our results, the baseline ECOG PS can be considered a prognostic factor for both PFS and OS. In conclusion, elderly pts should not be precluded from an active treatment and careful patient selection, mainly according to baseline ECOG PS, should guide treatment indication.