The discrepancies in the provision of quality health care services and adherence to patient safety in Illinois have been widely reported. This study investigated the situation by analyzing the available data with an objective of identifying the factors associated with poor patient safety and quality profile in the region. The impact of poor patient safety and quality was also investigated. Finally, strategies necessary for patient safety and quality enhancement in the region were identified. The study was carried out using a qualitative method based on case study approach. The study analyzed a total of 93 patient records in 5 hospitals in Illinois and 50 online case studies from 5 different databases recorded between the year 2006 and 2015. The data collection for this study was done from April 16, 2016 to April 29, 2016. The study results identified insufficient and unqualified workforce, lack of adequate equipment and patient-related factors to be associated with poor quality and patient safety to a significantly varying degree (P<0.05). Patient confidence, worsening of the clinical condition, trauma and occurrence of death were identified as some of the impacts of poor patient safety and quality. The study finally identified timely response to patient need, responsible leadership, adoption of advanced technology, collaboration with other health institutions and reduction of error as important strategies in patient safety and quality enhancement.