Introduction/objectives. Historical records describe a disease in North America that clinically resembled dengue haemorrhagic fever during the latter part of the Slave Trading period. However, the dengue epidemic that occurred in Cuba in 1981 was the first laboratory confirmed and clinically diagnosed outbreak of dengue haemorrhagic fever in the Americas. At that time, the predicted source of the dengue type 2 strain isolated during this epidemic was considered controversial, partly because of the limited sequence data and partly because the origin of the virus appeared to be Southern Asia.  The present research is aimed to characterize strains isolated at different time points during the epidemic. Material and methods. Complete viral genomes were amplified through five overlapping fragments using high fidelity enzymes. Full-length sequences were determined by automatic sequencing, and phylogenetic trees were constructed using a Bayesian method. Results.  The phylogenetic analysis showed that all Cuban strains isolated in 1981 are located grouped within the Asian 2 genotype, forming and independent group. In addition, the study revealed that viral evolution occurred during the epidemic; a fact that could be related to the month-to-month increasing severity. Moreover, the Cuban strains exhibited particular amino acid substitutions that differentiate them from the New Guinea C prototype strain as well as from dengue type 2 strains isolated globally. Conclusion. The molecular characterization of the causative agent of the 1981 epidemic at the entire genome level supported and extended previous findings concerning its genetic relatedness, denying the spreading of the virus from Cuba to Latin American countries as suspected during the 1980s.