Background: The primary aim was to assess Health Related Quality of Life (HRQoL), anxiety and depression in patients and caregivers during follow-up care after curative treatment for cancer in the pancreas, duodenum, or bile ducts. The secondary aim was to assess dyadic coping and the burden of being a caregiver. Materials and methods: In this prospective observational cohort study, we included patients and caregivers at first follow-up visit to conduct the following: Demographic characteristics, The European Organization for Research and Treatment of Cancer Quality of Life, the pancreas and bile duct module, EQ5D 3L, GAD-7 and PHQ-9 at baseline, and at six and nine-months follow-up visit. Demographic characteristics, Dyadic Coping Inventory and Zarit Caregiver Burden Questionnaire were conducted at baseline and at nine-months of follow-up visit. Results: The response rate was 42% with 104 of the 248 invited patients completing the questionnaires at baseline: 78 (75% of 104) after six and 69 (66% of 104) after nine months. The median (Q25,75) time for inclusion was 33.6 (13.4, 38) and 29.1 (18.3, 36) weeks after surgery for patients with pancreatic or duodenal cancer, and bile duct cancer, respectively. The response rate of caregivers was 88% with 75 of 85 completing the questionnaires. Fifty percent of patients with pancreatic or duodenal cancer had diarrhea at baseline. After six and nine months, this increased to 75%. Fatigue was the most prominent symptom in patients with bile duct cancer after nine months with 25% of patients scoring this as a clinical symptom. Conclusions: The study highlights the need to systematically screen physical and psychological symptoms in patients and caregivers during follow-up care after treatment for cancer in the pancreas, duodenum and bile ducts. Symptom management during follow-up care should be prioritized by clinicians.