Contrast reaction rates have been poorly studied with nonionic low osmolar agents. Premedication protocols to prevent contrast reactions to ionic high osmolar contrast have been studied in the past; however, protocol outcomes for the currently used nonionic low osmolar contrast is less clear. The purpose of this study was to evaluate the rate of contrast reactions with nonionic low osmolar using the standard premedication protocol as well as the effect of using a rapid premedication protocol. Retrospective single institution review of computed tomography (CT) scans from May 2011 through January 2022 was performed by searching the Cerner Soarian medical records system for patients with documented contrast allergies who received contrasted CT scans. The patients were then divided into groups depending on whether they received the 13-hour premedication protocol vs the 4-hour rapid protocol. Contrast reaction was extrapolated from administration of prednisone, hydrocortisone, diphenhydramine, or epinephrine outside of protocol within one hour with corresponding indication in the ordering system. Basic statistical analysis including χ2 testing was performed on acquired data. We performed 2588 premedicated contrasted CT cans during the study period, 2102 (81.2%) of which underwent the 13-hour premedication protocol and 486 (18.7%) underwent 4-hour premedication protocol. The average age of the 13-hour group was 62 years (range, 11-92) years and 1345 (64%) were female and the 4-hour protocol had an average age of 61 years (range, 5-92 years) and 277 (57%) were female. In the 13-hour group, there was an overall contrast reaction rate of 29% (613): 124 patients received prednisone, 107 hydrocortisone, 388 diphenhydramine, and 3 epinephrine. In the 4-hour group, 44% (214) patients had a contrast reaction: 78 received prednisone, 89 hydrocortisone, 41 diphenhydramine, and 6 epinephrine. There was significantly more treatment for contrast reaction in the 4-hour protocol group (P < .01). Protocols for premedication to prevent contrast allergy reactions have been based on ionic high osmolar contrast usage and have not been separately validated for use with nonionic low osmolar contrast agents. This study demonstrates that the preexisting protocols appear only partially effective in preventing contrast reactions and the outcomes for the rapid 4-hour protocol performed significantly worse than the standard protocol. These outcomes show the need for further study and protocol refinement as well as continued vigilance for contrast reactions while using the current protocols.