People in southern Taiwan experienced two major dengue outbreaks in 2014 and 2015. The mortality and clinical features were very different between these 2 years. Dengue virus serotype 1 (DENV-1) caused epidemic outbreak in 2014 and DENV-2 was predominant in 2015. The characteristics of dengue hemorrhagic fever (DHF) cases in the 2 years was analyzed. We conducted a retrospective chart review to analyze the clinical and laboratory features of 206 adult patients with DHF in southern Taiwan in 2014 and 2015. The mortality rate of DHF cases in 2015 was higher than that of cases in 2014 (38.7% versus 12.4%, P < 0.0001). Compared with cases in 2014, DHF cases in 2015 had more complications, such as gastrointestinal bleeding (78.5% versus 61.9%, P = 0.01), severe hepatitis (30.1% versus 8%, P < 0.0001), and myocarditis (14% versus 0.9%, P < 0.0001). Among the mortality cases, diabetes, chronic renal failure, proton-pump inhibitors using, platelet transfusion, and Charlson comorbidity index score (Charlson score) were also higher in 2015. Multivariate analysis for the mortality cases revealed that the risk factors were Charlson score ≥ 5 (P = 0.02, odds ratio [OR] = 4.07, 95% confidence interval [CI] = 1.244-13.307), severe hepatitis (P < 0.0001, OR = 11.97, 95% CI = 3.831-37.396), and acute renal failure (P < 0.0001, OR = 98.76, 95% CI = 10.847-899.22). DHF cases in 2015 had higher mortality and more complications, such as gastrointestinal bleeding, severe hepatitis, and myocarditis, than in 2014 in southern Taiwan. In the 2-year DHF case series, Charlson score ≥ 5, severe hepatitis, and acute renal failure were independent significant variables for mortality.