Theophylline is a bronchodilator drug that is used in the treatment of asthma and chronic obstructive pulmonary diseases. Cardiovascular complications contribute to morbidity and mortality that associate acute theophylline intoxication. The current study aimed to investigate troponin I and creatine kinase-MB as predictors of the severity and outcomes in cases of acute theophylline intoxication. This prospective cohort study included thirty one patients with acute theophylline toxicity admitted to Tanta Poison Control Center during the period from the first of March 2018 to the end of February 2019. Patients were subjected to personal and toxicological history taking, vital signs collection, grading of acute theophylline toxicity and measurement of serum theophylline level. Both troponin I and creatine kinase-MB were measured at admission and 12 hours post admission. Results revealed that, troponin I at time of admission and 12 hours post admission in addition to creatine kinase-MB 12 hours post admission were significantly higher in cases with severe acute theophylline intoxication and patients who required intensive care unit admission. It was concluded that, troponin I could predict the severity and the requirement of intensive care unit admission in acute theophylline toxicity either with early or delayed presentation. On the other hand, creatine kinase-MB could be considered for patients with delayed presentation.