Prevention of malaria in travelers to endemic countries is one of the complex challenges of travel medicine. Israel has a widespread culture of travel to developing countries, but information regarding malaria prevention is limited so far. Our study, conducted in Sheba Medical Center, Israel, during the years 2008-2018 examined malaria chemoprophylaxis usage and malaria cases in a large group of Israeli travelers returning from endemic countries with any medical complaint. Data were collected regarding travel destinations, conditions, duration of stay, and pretravel consultation. Altogether, 4,708 travelers were included in our study. Travel destinations included Asia (51%), Latin America (31%), and sub-Saharan Africa (SSA) (17%). Median travel duration was 26 days. Only 11.9% reported taking malaria chemoprophylaxis. Of the travelers to SSA, 41.3% took prophylaxis as opposed to only 6% outside of Africa. During the study years, 136 cases of malaria were diagnosed; among them, 82 (60%) were infected with Plasmodium falciparum, of whom all but two were from SSA and none adhered to prophylaxis. Malaria chemoprophylaxis usage was found to be negligible in travel to many countries still considered endemic. Higher prophylaxis usage was found among travelers to SSA, but numbers are still lower than recommended. The low number of malaria cases seen in destinations outside SSA, as documented in our cohort, is likely to represent travel to low risk areas and not high prophylaxis usage. We urge re-evaluation of current CDC and Israeli guidelines which still recommend using chemoprophylaxis in many low-risk countries, as focus on high-risk countries may increase adherence.