Background: Regional hyperthermia (RHT) with cisplatin added to gemcitabine showed efficacy in gemcitabine-pre-treated patients with advanced pancreatic ductal adeno- carcinoma. We conducted a randomised clinical trial to investigate RHT with cisplatin added to gemcitabine (GPH) compared with gemcitabine (G) in the adjuvant setting of resected pancreatic ductal adenocarcinoma. Methods: This randomised, multicentre, open-label trial randomly assigned patients to either GPH (gemcitabine 1000 mg/m2 on day 1, 15 and cisplatin 25 mg/m2 with RHT on day 2, 3 and 15,16) or to G (gemcitabine 1000 mg/m2 on day 1,8,15), four-weekly over six cycles. Disease- free survival (DFS) was the primary end-point. Secondary end-points included overall survival (OS) and safety. Results: A total of 117 eligible patients (median age, 63 years) were randomly allocated to treatment (57 GPH; 60 G). With a follow-up time of 56.6 months, the median DFS was 12.7 compared to 11.2 months for GPH and G, respectively (p= 0.39). Median post- recurrence survival was significantly prolonged in the GPH-group (15.3 versus 9.8 months; p= 0.031). Median OS reached 33.2 versus 25.2 months (p= 0.099) with 5-year survival rates of 28.4% versus 18.7%. Excluding eight patients who received additional capecitabine in the G- arm (investigators choice), median OS favored GPH (p= 0.052). Adverse events CTCAE (Common Terminology Criteria for Adverse Events) grade >=3 occurred in 61.5% (GPH) versus 63.6% (G) of patients. Two patients in the G-group died because of treatment- related toxic effects. Conclusions: The randomised controlled Hyperthermia European Adjuvant Trial study failed to demonstrate a significant difference in DFS. However, it showed a difference in post- recurrence survival and a strong trend for improved OS. Regional hyperthermia (RHT) with cisplatin offers innovative treatment options in PDAC. Clinical trial information: NCT01077427.