Aseptic meningitis is one of the most common neurological disorders caused by enteroviruses. Among them, Echovirus 30 (E30) is described as the main etiological agent of many outbreaks and sporadic cases. This study investigated the genomic variability of E30 isolated from the cerebrospinal fluid (CSF) of aseptic meningitis cases that occurred from 1998 to 2008 in Brazil. Over a 10-year period (1998–2008), 302 non-polio enteroviruses were isolated, of which 177 were identified as E30 (58.6%). Phylogenetic analysis of the complete VP1 gene (876 nt) of 48 E30 isolates was performed and compared with additional Brazilian and foreign strains. E30 VP1 sequences segregated into three distinct major groups and seven subgroups, which were linked to the isolation year. In general, sequence divergence among E30 strains ranged from 0.2% to 13.8%. A common direct ancestor for this set of E30 strains was not defined. Brazilian isolates from Group I were related genetically to a 1997 USA isolate and both may have a common origin. Group III representatives showed close relationship to the 2007 Argentinean isolates. The present results complement existing data on the molecular characterization and genetic variability of E30 and may contribute to the understanding of the epidemiology of aseptic meningitis in the region. J. Med. Virol. 83:2164–2171, 2011. © 2011 Wiley Periodicals, Inc.