The objectives of this investigation were to examine the travelers' knowledge, attitudes, and behavior about travel-related diseases and to evaluate the factors that influence their knowledge, attitudes, and behavior. A cross-sectional study was performed between May and September 2018 among a random sample of individuals attending randomly selected travel agencies in the geographical areas of Caserta and Naples, Italy. One fourth of participants (25.6%) had a poor level of knowledge, 50.2% a moderate, and only 24.2% a good level about the most common infectious diseases in the destination country. Those who had received information from physicians about the most common infectious diseases in the destination country and who do not need additional information were significantly more likely to have a good level of knowledge. A large majority (91%) showed no concern about the risk of getting an infectious disease during the travel. Almost half of the respondents had received information concerning the most common infectious diseases in the destination country and the related prevention measures. This information was more likely acquired by those graduated, those who know the foods that can cause the infectious diseases, and those who self-perceived a well health status, and less likely by those who had a poor level of knowledge about the most common infectious diseases in the destination country and who were going to Asia and South America. Education and communication activities regarding all aspects of travel-related diseases are needed to increase the knowledge and the access to preventive measures.