Background: The standard method for diagnosing Meckel diverticulum and identifying ectopic gastric mucosa is 99 mTc-pertechnetate imaging. Premedication with H2 receptor antagonists enhances the scan’s sensitivity by reducing the washout of 99 mTc-pertechnetate activity from the intestinal lumen. Objective: After the withdrawal of ranitidine, we compared the efficacy of the proton pump inhibitor pantoprazole as an alternative premedication agent for 99 mTc-pertechnetate Meckel diverticulum imaging. Materials and methods: This study assessed the scan quality of 141 children (aged 1 month to 204 months (median = 84 months)) who underwent Meckel scintigraphy over 10 years at a single institution. Before its withdrawal in December 2020, ranitidine was utilized for premedication, while pantoprazole was used thereafter. Therefore, patients were divided into two premedication groups: ranitidine (n = 88) and pantoprazole (n = 53). A high-quality scan was defined as having no 99 mTc-pertechnetate activity in the duodenal and other intestinal lumens. The effectiveness of pantoprazole in reducing 99 mTc-pertechnetate release in the duodenum and other intestinal lumens was compared to that of ranitidine. Differences in scan quality between the groups were analyzed using the two-proportion Z-test. In patients with positive scans, the lesion-to-background activity ratio of the Meckel diverticulum was measured and compared between the premedication groups. Results: Premedication with pantoprazole resulted in 47.2% of scans showing no 99 mTc-pertechnetate release, 37.7% with activity localized either in the duodenum or other intestine, and 15.1% exhibiting activity in both regions. In comparison, ranitidine resulted in 45.5% of scans with no 99 mTc-pertechnetate release, 40.9% with activity localized either in the duodenum or other intestine, and 13.6% showing activity in both regions. P-values were not found to be significant in all comparisons. Twelve scans were positive; all patients had Meckel diverticulum confirmed at surgery. For positive scans, the lesion-to-background activity ratio for the Meckel diverticulum was similar between the ranitidine and pantoprazole groups. Conclusion: This study demonstrates that pantoprazole is statistically non-inferior to ranitidine regarding scan quality and lesion-to-background activity ratios for Meckel diverticulum detection. Pantoprazole offers a reliable alternative for clinical protocols in the absence of ranitidine.