Background: Surgical site infection (SSI) includes infections occurring after 48 hours of any surgery and accounts for most of the healthcare-associated infections (HAIs) in surgical centers. Surgical site infections can result in pain, discomfort, prolonged hospital stay, increased exposure to antimicrobials, and consequentially, increased healthcare costs. Objectives: The study intended to characterize the incidence, etiology, and emerging resistance of SSI in a 1000-bed tertiary-care teaching hospital in New Delhi. Methods: The ambispective study was conducted in a 1000-bed tertiary-care teaching hospital in New Delhi. Clinical, laboratory, and environmental surveillance and screening of health care providers (HCPs) were conducted using the National Healthcare Safety Network (NHSN) definitions and methods given by the US Centers for Disease Control and Prevention (CDC). Results: With 3,541 patients admitted to the Gynecology and Obstetrics Ward and General Surgical Ward of the hospital, the total episodes of SSI were 80 (2.26%). The mean rates of superficial, deep, and organ space SSI were 46.25%, 47.5%, and 6.25%, respectively. The most common organisms isolated were Acinetobacter baumannii (23.75%), Pseudomonas aeruginosa (17.5%), Escherichia coli (15%), and Staphylococcus aureus (12.5%). Conclusions: The rate of SSI in our study was comparable to the unadjusted rates in India, lower-middle, upper-middle, and high-income countries worldwide. Patients with pre-existing medical illness, prolonged operation time, and wound contamination are strongly predisposed to surgical site infection.