Study objective: The benefit of Advanced Cardiac Life Support (ACLS) medications during cardiac resuscitation is uncertain. The objective of this study was to determine whether the use of these medications increased resuscitation from in-hospital cardiac arrest. Methods: A prospective cohort of patients undergoing cardiac arrest in 1 of 5 academic hospitals was studied. Patient and arrest factors related to resuscitation outcome were recorded. We determined the association of the administration of ACLS drugs (epinephrine, atropine, bicarbonate, calcium, lidocaine, and bretylium) with survival at 1 hour after resuscitation. Results: Seven hundred seventy-three patients underwent cardiac resuscitation, with 269 (34.8%) surviving for 1 hour. Use of epinephrine, atropine, bicarbonate, calcium, and lidocaine was associated with a decreased chance of successful resuscitation (P <.001 for all except lidocaine, P <.01). While controlling for significant patient factors (age, gender, and previous cardiac or respiratory disease) and arrest factors (initial cardiac rhythm, and cause of arrest), multivariate logistic regression demonstrated a significant association between unsuccessful resuscitation and the use of epinephrine (odds ratio .08 [95% confidence interval .04–.14]), atropine (.24 [.17–.35]), bicarbonate (.31 [.21–.44]), calcium (.32 [.18–.55]), and lidocaine (.48 [.33–.71]). Drug effects did not improve when patients were grouped by their initial cardiac rhythm. Cox proportional hazards models that controlled for significant confounders demonstrated that survivors were significantly less likely to receive epinephrine (P <.001) or atropine (P <.001) throughout the arrest. Conclusion: We found no association between standard ACLS medications and improved resuscitation from in-hospital cardiac arrest. Randomized clinical trials are needed to determine whether other therapies can improve resuscitation from cardiac arrest when compared with the presently used ACLS drugs. [van Walraven C, Stiell IG, Wells GA, Hébert PC, Vandemheen K, for the OTAC Study Group: Do Advanced Cardiac Life Support drugs increase resuscitation rates from in-hospital cardiac arrest? Ann Emerg Med November 1998;32:544-553.]