OBJECTIVES: Antibiotic resistance is considered a main public health concern. The price of new antibiotics must be sufficient to recover the investment. This study assessed trends in the cost per course of therapy of new systemic antibiotics approved by the FDA in the period 1999-2016. METHODS: A list of new antibiotics marketed in the US in the period 1999-2016 was extracted from the FDA webpage. Average wholesale prices (AWP) were extracted from the RedBook (Truven Health). Daily doses and duration of the treatment were extracted from the FDA-approved label. The AWP cost per course of antibiotic drug therapy were calculated. Prices were adjusted by the consumer price index to 2016 dollars. The compound annual growth rate (CAGR) was calculated for each price from market entry to December 31, 2016. Descriptive analysis were done in the study using Excel 2013. RESULTS: The FDA approved a total of 19 new systemic antibiotics in the period 1999-2016. The antibiotics had an average±standard deviation of 3.0±2.1 indications (range 1-8). Price information was available for all drugs with the exception of obiltoxaximab (2016). The cost of a course of drug therapy at market entry varied by drug, indication and population subgroup. The median cost per course of drug therapy was $1,305.64. Gatifloxacin had the lowest CPI-adjusted cost per course of drug therapy at market entry ($50.09 in 1999) and avibactam/ceftazidime had the highest cost (range: $1,801.10-$5,043.08 in 2015). The median cost of a course of drug therapy at market entry was $136.41 (range: $50.09-$1,639.74) in the period 1999-2004, and $1,703.81 ($538.75-$5,401.45) in the period 2005-2016. The CPI-adjusted median AWRP CARG was 6.91%. CONCLUSIONS: Prices of antibiotics at market entry increased during the study period. The prices of the marketed antibiotics also increased faster than the inflation.