BACKGROUND Due to rising life expectancy of population, very complex surgical procedures such as pancreaticoduodenectomy (PD), are more commonly being performed in elderly patients. The objective of this study was to evaluate the safety of PD in patients older than 75 years old and the risk factors associated with severe complications. METHODS Patients who underwent PD for periampullary tumors were retrospectively reviewed and divided into two groups, A (<75 years) and B (>75 years). The primary endpoint was severe postoperative complications (Clavien 3 or greater). Secondary endpoints were mortality and any complications. RESULTS Ninety consecutive patients underwent PD for periampullary tumors in the studied period, 70 in group A and 20 in group B. Clinical and pathological characteristics of both groups were equivalents except for age. There were no difference regarding the incidence of severe complications (17% vs. 10%, P=0.72) or all complications (50% vs. 50%, P>0.999). Although mortality was greater in group A (8.6% vs. 0%), it was not statistically significant (P=0.333). On multivariate analyses, only male sex, obesity and American Society of Anesthesiology Score of 3 or 4 were associated with severe postoperative complications. CONCLUSIONS Poor clinical status, obesity and male gender are associated with severe complications in PD, but not age greater than 75 years, therefore PD can be considered safe in elderly patients and age itself should not be a contraindication for PD.