Background: Postoperative pulmonary complications (PPCs) are frequent causes for adverse outcomes after major surgeries. Aim: The aim of this study was to compare the perioperative factors influencing the incidence of PPCs in two groups of patients undergoing prolonged major surgeries, namely head-and-neck versus abdominal surgeries, receiving postoperative ventilation. Patients and Methods: This prospective observational study was designed, and the necessary data were collected from consecutive patients fulfilling all criteria in a single center between August 2017 and March 2018. Correlation of PPCs with duration of surgery, perioperative mechanical ventilation (PMV), and volume of crystalloids used in both the groups was analyzed by multiple binary logistic regression. The inhospital mortality and number of days of intensive care unit (ICU) and hospital stay were analyzed with Student's t-test. Results: A total of 155 patients were studied in which 77 patients who underwent head-and-neck surgeries (Group 1) and 78 who underwent abdominal surgeries (Group 2). Both the groups had a comparable demographic profile. Group 2 patients had a higher incidence of PPCs. Duration of PMV but not of surgery influenced the occurrence of PPCs independently, showing 8.2% (1.2%-15.7%) increase in PPCs with every hour increase in PMV (odds ratio: 1.08 [95% confidence interval, 1.01-1.16] with P = 0.002). PPCs prolonged the ICU and hospital stays and mortality. Conclusion: Duration of PMV is an independent risk factor for the development of PPCs. Abdominal surgeries proved to be an independent risk factor for PPCs. Early identification and risk modifications are required to reduce PPCs in high-risk category of patients who receive general anesthesia with prolonged mechanical ventilation.