Background: Pancreatic cancer incidence in India is low. Over the years, refinements in technique of pancreatoduodenectomy (PD) may have improved outcomes. No data is available from India, South- Central, or South West Asia to assess the impact of these refinements. Purpose: To assess the impact of service reconfiguration and standardized protocols on outcomes of PD in a tertiary cancer center in India. Methods: Three specific time periods marking major shifts in practice and performance of PD were identified, viz. periods A (1992e2001; pancreaticogastrostomy predominantly performed), B (2003eJuly 2009; standardization of pancreaticojejunal anastomosis), and C (August 2009eDecember 2011; introduction of neoadjuvant chemo-radiotherapy and increased surgical volume). Results: 500 PDs were performed with a morbidity and mortality rate of 33% and 5.4%, respectively. Over the three periods, volume of cases/year significantly increased from 16 to 60 (p < 0.0001). Overall incidence of post-operative pancreatic anastomotic leak/fistula (POPF), hemorrhage, delayed gastric emptying (DGE), and bile leak was 11%, 6%, 3.4%, and 3.2%, respectively. The overall morbidity rates, as well as, the above individual complications significantly reduced from period A to B (p < 0.01) with no statistical difference between periods B and C. Conclusion: Evolution of practice and perioperative management of PD for pancreatic cancer at our center improved perioperative outcomes and helped sustain the improvements despite increasing surgical volume. By adopting standardized practices and gradually improving experience, countries with low incidence of pancreatic cancer and resource constraints can achieve outcomes comparable to highincidence, developed nations. Synopsis: The manuscript represents the largest series on perioperative outcomes for pancreatoduodenectomy from South West and South-Central Asia e a region with a low incidence of pancreatic cancer and a disproportionate distribution of resources highlighting the impact of high volumes, standardization and service reconfiguration.