Dengue virus-type 2 (DENV-2) caused three outbreaks, in the years 1990, 1998, and 2008, in Rio de Janeiro, Brazil. The 2008 outbreak was the most severe in reported cases, hospitalizations, and deaths. To investigate virological and epidemiological factors that may have contributed to the pathogenic profile of 2008 epidemic, 102 patients sera obtained during the epidemic and inter-epidemic periods of three outbreaks were analysed by qRT-PCR to estimate viremia levels and their correlation with the clinical, immunological, and demographic patient characteristics. DENV-2 isolates from the outbreaks were sequenced. Two DENV-2 lineages (I and II) of the American/Asian genotype were confirmed, each exclusive for 1990-2002 and 2007-2011, respectively. The mean viremia level in the 2008 samples was two orders of magnitude higher than that of the 1990-2002 samples. Severe dengue cases increased from 31% in 1990-2002 to 69% in 2007-2011; in patients aged ≤15 years, from 3% in 1990-2002 to 37% in 2007-2011. The DENV-2 lineage II and younger age significantly contributed to the pathogenic profile of 2008 epidemic in Rio de Janeiro.