Sodium nitrite and sodium thiosulfate are common cyanide antidotes. Hydroxocobalamin was approved for use in the United States in 2006. Our objective was to determine the frequency of antidote use as reported to the US poison centers from 2005 to 2009 and describe which antidotes were used in critically ill cyanide toxic patients. We performed a retrospective review over 5 years (2005-2009) from 61 US poison centers. We identified all cyanide-exposed cases that received a cyanide antidote. Variables collected included demographics, gastric decontamination, antidote used, predefined serious clinical effects (hypotension, cardiac arrest, respiratory arrest, and coma), and predefined serious therapies (cardiopulmonary resuscitation, vasopressors, atropine, anticonvulsant, antidysrhythmic, and intubation/ventilation). One trained abstractor abstracted each chart to a standardized electronic form. Another investigator audited 20% of the charts. Kappa values were calculated. One hundred sixty-five exposures were identified. Mean age was 42 years (range, 3-93 years). Seventy-one percent were male. Exposures were 27% ingestion and 53% inhalation. Thirty-two percent of the ingestions were suicide attempts. Twenty percent (32 of 157) of all cases died. Over all years reported, hydroxocobalamin was administered to 29% (45 of 157) of patients, sodium nitrite to 25%, and sodium thiosulfate to 46%. Hydroxocobalamin use increased from 24% to 54% from 2007 to 2009, respectively (P = 0.024). Sodium thiosulfate use decreased from 73% to 31% (P = 0.002) and sodium nitrite use decreased from 26% to 14% (P = 0.39). The proportion of cases with serious clinical effects that received hydroxocobalamin increased each year, and the proportion that received other antidotes decreased. Hydroxocobalamin was also administered more often in cases that required serious therapies and increased each year. Hydroxocobalamin use for cyanide toxicity increased each year as reported to the US poison centers. Reported use of sodium thiosulfate and sodium nitrite decreased over the same years. In addition, hydroxocobalamin was used more often each year in critically ill cyanide toxic patients than were sodium nitrite or sodium thiosulfate.