Review of toxicology screening results in our level 1 trauma center revealed that approximately 15% of urine drug screens were positive for cocaine metabolite. Our objective was to determine the prevalence of true acute cocaine intoxication and if measurement of serum would improve upon the accuracy of toxicology screening for identifying acute cases of cocaine poisoning. Cases were analyzed for cocaine metabolite (benzoylecgonine, BE) in matched serum and urine specimens and for acute cocaine intoxication by retrospective chart review. BE was identified in 3.8% of serum and 14.6% of urine specimens. For the identification of the acutely poisoned patient, the predictive value of toxicology screening was 53.4% for serum and 17.8% for urine. Of patients who screen positive for BE in serum, the odds of intoxication are 44:1 (95% CI 4.85-396.7). We conclude that subjects who test positive for BE in serum have a high probability of acute cocaine intoxication and that analyzing serum improves the predictive value of testing by 3-fold.