Background: Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers. KRAS, TP53, CDKN2A and SMAD4 are established driver genes in PDAC. We aimed to determine if the mutational status of these 4 driver genes, and other frequently altered genes, are predictive of clinical outcomes in patients who undergo resection. Methods: Patients who underwent resection of PDAC and consented to targeted sequencing of their primary tumor using MSK-IMPACT, were included. Genomic alterations were determined based on MSK-IMPACT sequencing results of formalin-fixed, paraffin-embedded tumor. A prospectively maintained database and electronic medical record were queried for clinical and pathologic variables. Gene mutation status was compared with overall survival (OS) and recurrence free survival (RFS) using the log-rank test, and with pathologic variables using Wilcoxon rank-sum and Fisher’s exact tests. Results: Targeted genomic sequencing was performed on N = 285 primary tumors resected between 2004-2017. N = 55 (19%) patients received neoadjuvant therapy prior to sequencing and N = 220 (77%) received adjuvant therapy. Median OS was 39 months with a median follow up of 22 months. Frequency of genomic alterations and their association with OS and RFS are shown in Table 1. Alterations in both KRAS and TP53 were associated with worse OS, but not RFS, as compared to wildtype. Mutant KRAS was also associated with larger tumor size (median, 3.0 vs 2.2cm, p = 0.009). Conclusions: Alterations in KRAS and TP53 were associated with worse OS in patients with resected PDAC. Further analysis will include the association of driver gene variants, as well as other gene alterations, with clinical and pathologic outcomes.