Background Scope-induced duodenal perforation is a life-threatening complication and surgery remains the standard of care. With the advent of over-the-scope clip (OTSC), scope-induced perforations are increasingly managed conservatively, though there is no study comparing this form of non-surgical treatment with surgery. We aimed to compare OTSC and surgery in the management of scope-induced perforation of the duodenum. Methods We retrospectively collected data of scope-induced duodenal perforation patients. Perforations identified and treated within 24 h of procedure were analyzed. Factors analyzed were spectrum, etiology, baseline parameters, perforation size, outcome, comorbidities, and duration of hospital stay. Results A total of 25 patients had type I duodenal perforations, out of whom five were excluded due to delayed diagnosis and treatment. Of the twenty, eight were treated with OTSC placement while the rest underwent surgery. Age was comparable and the majority were females. Baseline parameters and comorbidities were similar in both the groups. The median size of perforation was 1.5 cm in both the OTSC group and the surgical group. All patients were treated with standard of care according to institutional protocols. Patients in the OTSC group were started orally after 48 h of OTSC placement, while in the surgery group median time to oral intake was 7 days. Two patients in the surgical group died while there was no mortality in the OTSC group (p = 0.48). Median hospital stay was shorter in the OTSC group (2 days vs. 22 days, p = 0.003). Conclusions OTSC is a feasible and better option in type I duodenal perforations with a shorter hospital stay.