Background: Patients with pancreatic cancer run a considerable risk of disease progression or, after resection, disease recurrence, ultimately leading to death. Therefore, it is plausible that pancreatic cancer patients experience fear of cancer recurrence or progression (FOP). The aim of this study was to compare FOP in patients with pancreatic cancer treated with surgery, palliative systemic treatment or best supportive care (BSC), and examine the association between quality of life (QoL) and FOP and between FOP and overall survival (OS), respectively. Methods: This prospective multicenter cohort study included patients diagnosed with pancreatic cancer between 2015 and 2018, who participated in the Dutch Pancreatic Cancer Project (PACAP). Data on FOP (worry of cancer progression scale [WOPS]) and QoL (EORTC QLQ-C30 summary scale score), were obtained from the PACAP database. Data regarding patient and tumor characteristics were derived from the nationwide Netherlands Cancer Registry. The association between QoL and WOPS was assessed with logistic regression analysis. OS was evaluated using Kaplan Meier curves with log-rank test and multivariable Cox proportional hazard analyses. Results: In total, 315 patients were included, of whom 111 patients underwent surgery, 138 received palliative systemic treatment, and 66 BSC. WOPS scores tended to decrease and stabilize over time in all subgroups. Patients who underwent surgery had significantly lower WOPS scores (i.e. less FOP) at initial diagnosis compared to patients in the palliative systemic treatment and BSC group (p = 0.004). Higher QoL scores were independently associated with a lower probability of high WOPS scores in patients receiving BSC only (OR 0.95, P = 0.006). Baseline WOPS score was not independently associated with OS. Conclusions: Pancreatic cancer patients reported FOP at diagnosis, which decreased and stabilized over time. Given the distress that FOP evokes, FOP should be explicitly addressed by health care providers when guiding pancreatic cancer patients through their treatment trajectory, especially those receiving palliative treatment or BSC.