Reported here is a predominant clone of Neisseria meningitidis B:14:P1.13 that persisted over a 6-year period in the northernmost province of Italy, where it was responsible for a higher incidence of meningococcal disease compared to the rest of the country. Genetic relatedness of isolates was confirmed by multilocus sequence typing, pulsed-field gel electrophoresis and PorA variable region typing. All strains examined belonged to the ST44 complex/lineage III. Risk factors for infection were evaluated through a case-control study conducted with 21 cases and 63 age- and sex-matched controls. Risk factors for infection in the seven patients younger than 13 years were (i) residence in a rural area, (ii) exposure to passive smoke, and (iii) living in a home with rooms rented to tourists (all odds ratios infinite). The only risk factor for the older patients was previous influenza-like illness (odds ratio, 41.9; 95% confidence interval, 1.6-1068.9). Guidelines for the early treatment of patients and public information campaigns were successfully implemented to reduce disease transmission and the case fatality rate in the region.