Background: The creation of a joint between two bowel ends in newborns and infants is one of the core surgical procedures in pediatric surgery. For a proper and perfect gastrointestinal (GI) anastomosis, the factors to be considered are intraoperative duration, restoration of normal GI function, effective hemostasis, reduction of tissue damage, and prevention of postoperative mortality and morbidity. The safety and efficacy of stapled GI tract anastomosis in adults have been extensively documented; however, available literature on the same is limited for infants. Materials and methods: Fifty-six patients were divided into two groups—stapled group and hand-sewn group. Patients operated on both emergency and elective basis were included in the study. Hand-sewn anastomosis was done by either end-to-end single-layer or double-layer anastomosis. Suture material used for the anastomosis was Vicryl 3-0 or Vicryl 4-0. Stapled anastomosis was done by 55 mm linear cutting GI stapler with side-to-side anastomosis. Results: The present study included a total of 56 patients; there were 28 neonates and 28 infants; 37 of them were males. The most common clinical presentations were vomiting, abdominal distention, refusal to feed, and lethargy. The intraoperative duration in stapled GI anastomosis was less when compared to hand-sewn anastomosis, so was the return of bowel activity and consequently early initiation of feeds and shorter hospital stay. Conclusion: The present study favors stapled over hand-sewn GI anastomosis in infancy in view of decreased intraoperative duration, reduced blood loss, early return of peristalsis, early initiation of feeds, and shorter duration of hospital stay. However, a small number of patients and lack of matching are the shortcomings of this study.