Data of all the cases of Invasive Meningococcal Diseases are collected in the frame of the National Surveillance System coordinated by the National Reference Laboratory (NRL) of the Istituto Superiore di Sanità, which performs further microbiological characterization on collected isolates. In Puglia, from 1994 through 2014, the average incidence was 0.2 per 100.000 inhabitants, lower than the national value (0.33), with a peak in 2013 of 0.46 per 100.000 inhabitants. Patients tended to be older (median age 19 vs16). The case-fatality rate was 20.4% in Puglia vs 13.3% in Italy. Serogroups B and C were the most identified. Fourty-seven percent of the isolates showed a decreased susceptibility to penicillin G. Serogroups C and Y presented a fairly clonal pattern, whereas serogroup B isolates were rather genetically heterogeneous. Surveillance system is essential to monitor possible changes in the epidemiology of invasive meningococcal disease consequent to immunization strategies adopted locally and nationally.