Phytonadione (vitamin K1) administered intravenously (i.v.) has been associated with anaphylaxis, although the incidence is not known. The anaphylaxis is thought to be attributable to the solubilizing vehicle, polyethoxylated castor oil (Cremophor EL, BASF AG, Ludwingshafen, Germany). To estimate the incidence of anaphylaxis after i.v. administration of phytonadione. A retrospective review of anaphylaxis after i.v. phytonadione over a 58-month period at a large academic center was performed. During the period of the study a protocol for the administration of i.v. phytonadione was in place. A review of computerized records and survey of staff identified cases of anaphylaxis meeting predefined inclusion criteria. In addition, a literature review was performed for articles concerning anaphylaxis after i.v. phytonadione. Over the 58 months of the study, a total of 6,572 doses of i.v. phytonadione were administered. Two cases of anaphylaxis after i.v. phytonadione were identified. The incidence of anaphylaxis was 3 per 10,000 doses with 95% confidence intervals of 0.04 to 11 per 10,000 doses. The literature review identified 14 cases meeting inclusion criteria with no reviews of the literature or estimates of incidence. The incidence of anaphylaxis after i.v. phytonadione is overall comparable or slightly less than other drugs known to cause anaphylaxis. We do not recommend routine pretreatment with antihistamines or corticosteroids before administration of phytonadione.