OBJECTIVES: Shortages of antibiotics adversely impact health outcomes and health care costs. We assessed the prevalence of shortages of systemic antibiotics and evaluated the characteristics of the antibiotics in short supply as reported by federal agencies and private health care providers in the US on June 1, 2011. METHODS: Data were collected from the FDA, American Society of Health-System Pharmacists (ASHP), and Brigham and Women’s Hospital (BWH) websites. The units of analysis were active ingredient(s) and route of administration. The prevalence of shortages was estimated as a percentage of the total number of products in the US market as of June 1, 2011. RESULTS: A total of 18 antibiotic active ingredients with 20 routes of administration were in short supply as of June 1st, 2011. The prevalence of shortages of systemic antibiotics varied from 20.6% reported by ASHP to 3.1% reported by the FDA and BWH. Injectable antibiotics had the highest (28.3%) rate of shortage followed by oral products (11.4%). Three shortages were resolved as of December 31, 2011. The average duration of shortage as of Dec-31-2011 was 589.2±304.6 days. The average number of companies marketing the products in short supply was 5.4±3.1, with 5 products having only 1 manufacturer. Generic products were available for 95.0% of the drugs. The brand name product was discontinued for 55.0% of the drugs. The drugs in shortage had an average of 2.3±1.0 shortages from 2001 to 2011. Shortages resulting from discontinuation occurred because of problems with manufacturing (35.0%), raw materials (15.0%), FDA regulatory issues (5.0%), and for unknown reasons (45.0%). CONCLUSIONS: Over one-fourth of the injectable systemic antibiotics available in the United States were reported in short supply. Problems with manufacturing and raw materials represented most of the reported causes of shortages. Additional research is needed to assess the risk factors and causes of pharmaceutical shortages in the United States.