Background In the last few years, Malta has witnessed increasing immigration flows from the Libyan coasts. Public health policies are focused on screening migrants for tuberculosis, whereas no systematic actions against STIs are implemented. The aim of this study is to define the epidemiological profile of asylum seekers in Malta as regards syphilis, hepatitis B, C and latent tuberculosis, thus supporting screening policies. Methods Five hundred migrants living in open centres were screened between December 2010 and June 2011. Results 83.2% of people was from Somalia, 81.2% males, average age 26.5 years. The tuberculin skin test (TST) was positive in 225 migrants (45%). Latent syphilis was diagnosed in 11 migrants, hepatitis C in 3 and 31 migrants were HBsAg positive. Conclusion Systematic screening for asymptomatic migrants in Malta is not recommended for hepatitis C and syphilis, given the low prevalence observed. On the contrary, it should be considered for hepatitis B. TST could be indicated as the first step of a two step screening for migrants from countries with high TB incidence. Efficacy and cost-effectiveness could be achieved by further targeting screening to specific subgroups at higher risk of reactivation, such as people living with HIV and subjects affected by chronic diseases.