<p>Perforation peritonitis is a life-threatening abdominal emergency requiring prompt surgical intervention. Accurate risk stratification tools are essential for predicting mortality and guiding clinical decision-making. This study compares the predictive value of the Mannheim Peritonitis Index (MPI) and the POSSUM (Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity) scoring systems in patients undergoing emergency laparotomy for perforation peritonitis. A prospective, single-centre observational study was conducted at a tertiary care hospital in New Delhi from February 2024 to June 2025. Seventy adult patients with radiologically confirmed perforation peritonitis undergoing laparotomy were enrolled. MPI and POSSUM scores were calculated pre- or intra-operatively. Primary outcome was in-hospital mortality; secondary outcomes included wound infection, wound dehiscence, respiratory complications, anastomotic leak, ICU admission, ventilatory support, and hospital stay. Statistical analyses included ROC curves, logistic regression, and subgroup analysis. Mortality was significantly associated with higher MPI and POSSUM scores (<i>p</i> = 0.0002 and &lt; 0.0001, respectively). MPI showed stronger associations with wound-related complications and ICU needs, while POSSUM better predicted respiratory failure and mortality. Inconsistent performance of POSSUM in predicting wound dehiscence and anastomotic leaks was noted. Both MPI and POSSUM are effective tools for predicting outcomes in perforation peritonitis. MPI offers simplicity and utility in emergency settings, while POSSUM provides a more comprehensive physiological assessment. A combined scoring approach may enhance prognostic accuracy.</p>