Background: Cardiac catheterization is a medical procedure that helps doctors examine the heart and its blood vessels in detail. Cardiac catheterization has several complications that embrace the following: infection, injury, and pain at the Intra Venous site (IV) or sheath insertion site, blood clots, and harming urinary organs may occur because of the distinction dye common in kidney disease and patients with Diabetes Mellitus (DM). Ensuring patient safety, and preventing harm during healthcare, is crucial, especially after this procedure. Hence, the study aimed to evaluate the impact of instructional guidelines on patients' knowledge and anxiety regarding cardiac catheterization' complications. Subjects and method: Design: A quasi-experimental research design was used with a pre-and post-test. Setting: the research was conducted in the Cardiac Catheterization Unit. Subjects: A purposive sample of all 100 patients in two groups with 50 patients who were willing to participate in the study, and patients who were admitted were included and divided into two equal groups, the experimental group who received instructional guidelines and the control group received routine care instructions. Two tools were used: Tool (I) An interviewing questionnaire, which included two parts: (a) Personal data; (b) knowledge assessment data, and Tool (II) Spielberger's State-Trait Anxiety Inventory. Results: The results of this study revealed that there were significant differences in anxiety and knowledge level among patients undergoing cardiac catheterization in the control group compared with the experimental group after the instructional guidelines implementation at (P < .001), besides a lower incidence of complications among patients in the experimental group than in control group. Conclusion: The current study concluded that instructional guidelines implementation had a significant positive effect on improving knowledge and reducing anxiety levels and complications among the studied patients undergoing cardiac catheterization in the experimental group than control group and lower incidence of vascular complications among patients in the experimental group. Recommendations: Patients should be provided with sufficient information about cardiac catheterization, risk factors, and complications before discharge from the hospital,  Training program about complications for patients undergoing cardiac catheterization. The study should replicated on a large sample to generalize the results with replication of the current study with a larger sample