Poisoning and fatalities by cardiotoxic agents represent a challenging health problem in Egypt. An important action to combat this problem is to predict or, at least, early diagnose cardiac involvement. To do so, the clinician needs both bedside skills and appropriately selected laboratory testing. The Poisoning Severity Score (PSS) has been evaluated in one study which found it to be useful in identifying serious and complicated cases of poisoning. The aim of this study was to investigate effectiveness of the PSS in predicting cardiotoxicity, as well as correlations of different demographic, exposure, clinical and laboratory findings to cardiotoxicity. Methodology: Over a period of 4 months, we investigated 59 patients with anticholinesterases (n=28), digoxin (n=17), and beta-blocker toxicities (n=14) admitted to Poison Control Center of Ain Shams University Hospitals (PCCA), Cairo, Egypt, in addition to 16 healthy controls. For each, age, sex, mode of exposure, compound involved, time elapsed between exposure and admission, length of hospital stay, clinical, laboratory, and electrocardiographic findings were recorded. Also, PSS was calculated. Results: Female gender, lag between exposure and admission, length of ICU stay, and total length of hospital stay were significantly correlated to the severity of cardiotoxicity. Vomiting, metabolic acidosis, respiratory alkalosis, and PSS were independent predictors of cardiotoxicity. A PSS of 2 had a sensitivity of 88% and a specificity of 64.7% in predicating cardiotoxicity. Conclusion: Implication of PSS in prediction and early diagnosis of cardiotoxicity is easy, available, cheap, and reliable, whatever the type of toxic exposure.