OBJECTIVES: To compare price changes with time for Tumor Necrosis Factor (TNF) inhibitor agents in Israel and the USA and to comprehend if regulation influences price trajectories. METHODS: We studied the changes of prices for five anti-TNF agents, approved by the FDA between 1998 and 2009: infliximab, etanercept, adalimumab, golimumab and certolizumab. For US prices we used Average Sales Prices which are a baseline indicator for Medicare reimbursement. For Israeli prices we used the Maximum Retail Prices, regulated by the Ministry of Health. We presented all prices in US$ and also adjusted for inflation rates. For each drug we calculated the quarterly and cumulative price changes and compared trajectories between countries. RESULTS: With a median follow-up of 9 years, average cumulative changes in prices were +36% for the US and -22% for Israel. Significant differences between US and Israel in mean quarterly price changes were noted for infliximab (0.94 vs. -1.66 p=0.007), etanercept (2.03 vs. -1.48 p<0.0001) and adalimumab (2.27 vs. -1.73 p<0.0001). Similar non statistically significant trend (short follow-up) was seen for golimumab and certolizumab. CONCLUSIONS: There are significant differences in drug price trajectories between Israel and the US. This could be due to the fact that US Medicare is not legally permitted to negotiate prices, while in Israel there is a regulatory mechanism that is based on reference pricing. Without regulation, prices will likely continue to rise in the US as there is an inelastic demand for treatments. In order to retain a sustainable healthcare system, especially when dealing with chronic conditions, such as rheumatologic autoimmune diseases, mechanisms of drug price regulation must be considered.