Intravenous phenytoin has come under increased scrutiny with the introduction of the prodrug, fosphenytoin. We evaluated adverse events and length-of-stay using parenteral the two drugs in routine emergency department use. Open-label randomization of phenytoin or fosphenytoin in 256 Emergency Department patients prescribed 279 parenteral doses of a phenytoin-equivalent. All phenytoin was administered intravenously, and fosphenytoin was given intravenously or intramuscularly (physician preference). Adverse events and Emergency Department length-of-stay were recorded; re-presentation to the Emergency Department within three months was reviewed for evidence of the purple glove syndrome. Nonparametric statistics were used to analyze the data. Seventy-seven patients received phenytoin and 202 fosphenytoin; 28 (10.0%) received intramuscular fosphenytoin. The mean phenytoin-equivalent dose was similar between the groups. Eighteen patients required reduction in infusion rates because of an adverse event (phenytoin = 6.5%, fosphenytoin = 6.4%; OR 0.9, 95% CI 0.4 2.6; p = 1.0). Adverse events occurred with similar frequency (phenytoin 9.1%, fosphenytoin 15.8%; OR 0.7, 95% CI 0.3 1.4; p = 0.3). The most common events were: pruritus, pain on infusion, and paresthesias. One patient developed hypotension (fosphenytoin); there were no other serious adverse events, including phlebitis. Median Emergency Department length-of-stay was 6.7 h for phenytoin and 5.7 h for fosphenytoin (p = 0.6). In routine Emergency Department use, our data do not support formulary conversion from phenytoin to fosphenytoin, based on the incidence of adverse events or Emergency Department length-of-stay.