Background <p>Infantile hypertrophic pyloric stenosis (IHPS) is the most common surgical cause of non-bilious vomiting in infants, necessitating timely surgical intervention. Despite established treatment protocols, outcomes vary widely based on clinical and demographic factors.</p> Aim <p>This study aimed at assessing the factors determining the surgical outcomes in IHPS at Muhimbili National Hospital (MNH).</p> Methodology <p>This was a retrospective cohort study of 100 infants with intra-operatively confirmed IHPS who underwent pyloromyotomy between 2015 and 2024. Data on demographics, clinical presentation, biochemical markers, surgical details, complications, and outcomes were analyzed. Chi-square and multivariate logistic regression were applied to determine associations, with <i>p</i> &lt; 0.05 considered statistically significant.</p> Results <p>IHPS constituted 12.24% of all pediatric laparotomies. The median age was 45 days, with a male to female ratio of 4.3:1. Vomiting (100%), weight loss (17%), and visible gastric peristalsis (21%) were common presentations. Electrolyte imbalances were frequent: hypokalemia (64%), hyponatremia (58%), and hypochloremia (66%). Surgical complications occurred in 30% of infants, with a mortality rate of 6%. Significant factors associated with prolonged hospital stay included preterm birth (AOR = 8.05, <i>p</i> = 0.032) and low hemoglobin (<i>p</i> = 0.040).</p> Conclusion <p>IHPS is a common and surgically manageable condition in infancy. However, preoperative factors such as prematurity and anemia significantly affect outcomes. Strengthening preoperative optimization could improve survival and reduce hospital stay.</p>