- Purpose The abundant use of antibiotics (Abs) in the community plays a major role in inducing Ab resistance, but the literature concerning patterns in outpatient Ab use is limited. This study aims to lay the foundations for future policy and interventional programs to address the rise in Ab resistance by looking at long-term trends in Ab usage in Israel. Methods Defined daily doses per 1,000 inhabitants per day (DID) of total Ab use, consumption in different age groups, and of different Ab preparations were calculated for the years 2000, 2005, and 2010 in the eight districts of Israel. Data were collected from the pharmacy registries of “Clalit Health Services”, the largest Health Maintenance Organization (HMO) in Israel, covering 4 million patients, representing 53 % of the population. Trends in use over time were analyzed. Results The overall Ab usage in Israel has remained constant in the last decade. Three significant trends were identified in this study: an increase in the consumption of expensive, broad-spectrum Abs, paralleled by a reduction in narrow-spectrum Abs; an increase in Ab consumption among the elderly, counteracted by reduced usage among children; large regional variations in the overall and specific use of Ab agents. Conclusions Our main findings of increased broad-spectrum Ab consumption, primarily among the adult population in Israel, and a wide variability in Ab use between the regions in Israel, can focus our future studies on searching for the factors behind these trends to aid in constructing interventional methods for decreasing outpatient Ab overuse.