Background: The recurrence and liver metastasis rates are still high in pancreatic head cancer with curative surgical resection. A no-touch isolation principle in pancreaticoduodenectomy (PD) may improve this situation, however, the exact advantages and efficacy of these principles have not been confirmed. Materials and methods: Among 370 patients who underwent PD, three centers were selected and classified into two groups: the no-touch PD group (n = 70) and the conventional PD group (n = 300). Propensity score matching was used to control for selection bias at a ratio of 1:1. The confounding variables were age, sex, body mass index, adjuvant chemotherapy, carbohydrate antigen 19-9, tumor size and tumor differentiation. Results: Patients in the no-touch PD group had better overall survival (OS) and disease-free survival (DFS) than those in the conventional PD group (OS: 17 vs. 13 months, p = 0.0035, DFS: 15 vs. 12 months, p = 0.087), with lower 1- and 2-year disease-related mortality rates (1-year: 32.9% vs. 47%, p = 0.032; 2-year: 42.5% vs. 82% p = 0.000) and recurrence and liver metastasis rates (1-year: 30.0% vs. 43.3%, p = 0.041; 2-year: 34.3% vs. 48.7%, p = 0.030). Compared with the matched conventional PD group, the no-touch PD group also had a better OS (17 vs. 12 months, p = 0.032). Conclusions: Our study showed the no-touch isolation principle may be a better choice to improve long-term survival for pancreatic cancer patients.