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<p><b>INTRODUCTION: </b>The aim of this study is to analyze the evolution of pancreatectomy with venous resection in 10 referral Italian centers in the last 25 years.</p><p><b>METHODS: </b>A multicenter database of 425 patients submitted to pancreatectomy with venous resection between 1991 and 2015 was retrospectively analyzed. Patients were classified in 5 periods: 1 (1991-1995); 2 (1996-2000); 3 (2001-2005); 4 (2006-2010); 5 (2011-2015). Indications and outcomes were compared according to the period of surgery.</p><p><b>RESULTS: </b>Nineteen patients were operated in period 1, 28 in period 2, 91 in period 3, 140 in period 4, and 147 in period 5. Use of neoadjuvant therapy increased from 0% in period 1 and 2-12.1% in period 5. Postoperative complications ranged from 46.3% to 67.8%, and mortality from 5.3% to 9.2%. Median survival progressively increased, from 6 months in period 1-16 months in period 2, 24 months in period 3 and 4 and 35 months in period 5 (p = 0.004). Period, venous and nodal invasion were significant prognostic factors for survival.</p><p><b>CONCLUSION: </b>Management and outcomes of pancreatectomy with venous resection have evolved in the last 25 years in Italy. Improvement in patients' multidisciplinary management has lead to significant improvement of median survival.</p>