Malaria is the most common life-threatening infectious disease among travellers and chemoprophylaxis is recommended. The overall effectiveness, medication types and cost of malaria chemoprophylaxis in Accra are not well documented. This study investigated the use of chemoprophylaxis for malaria prevention in air travellers departing from Kotoka International Airport (KIA) in Accra, Ghana. A cross-sectional study was conducted in the departure lounge of the KIA between February and May 2012. A total of 424 respondents voluntarily completed a semi-structured questionnaire, which included socio-demographic characteristics, duration of stay, nationality, country of permanent residence, chemoprophylaxis used, number of doses missed, cost and side effects experienced, and cost of treatment. The mean age of respondents was 37 ± 0.84 years with a male:female ratio of 1.2:1.The mean duration of stay in Ghana was 47.9 days SD 56.8 and 73.5% had made one trip to the country in the preceding year. Of the respondents, 50.7% were from Europe, 24.1% from North America and 17.5% from Africa. The most popular malaria prevention method used was prophylactics (37%) with atovaquone/proguanil used most frequently (34.9%), followed by mefloquine (11.6%) and doxycycline (7.8%). Compliance was high: 73.8% of respondents did not miss a single dose. The most commonly reported side effects were dreams, abdominal discomfort and headaches. Malaria incidence was 7.1% with 80% of them receiving treatment in a hospital or clinic; incurring a cost of up to $30 to treat a person. Most air travellers from Accr a take atovaquone/pr oguanil. Malaria incidence was low and most travellers were compliant with their chemoprophylaxis with very few side effects. The cost of chemoprophylaxis is low and is thus recommended for all travellers to Accra, Ghana.