The U.S. Food and Drug Administration (FDA) uses the FDA Adverse Event Reporting System (FAERS) to monitor adverse events resulting from pharmaceutical drug use. However, this system has limitations such as not allowing real-time data collection. To address these limitations, the FDA launched the Sentinel Initiative in 2008. This comparative case study was conducted to describe perceptions of investigating the efficacy of the Sentinel Initiative compared with the FAERS. The study was based on the theory of preemption as it emphasized the need for efficient means for providing unquestionable proof that consumers suffered adverse drug effects. The sample included interivews of 20 individuals, who worked closely with the FAERS program and were familiar with the Sentinel Initiative. In-depth key-informant interviews had been conducted to determine the perceptions of the participants regarding the challenges and benefits of the Sentinel Initiative compared with FAERS. To analyze data, content analysis was used. The study concluded that the FAERS and Sentinel Initiative provided a systematic database, which included health data, that could be used to improve public health. Due to the FAERS and Sentinel Initiative, adverse effects of drugs will be recognized and the safety of the patients and the public will be prioritized. The findings of this study have potential social impact for positive change at the societal level, organizational level, and individual level in terms of overall safety of the drugs. Sentinel initiative at its present state complements the existing FAERS and leverage its benefits by connecting at a grass roots level patients to an organization level as well as stakeholders to make an impact in providing safer drugs on the market.