All patients with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL) and treated over a 17-year period at a single institution were retrospectively analyzed. From 1990 to 2000, 40 patients were treated with a variety of adult-based ALL regimens. From 2000 to 2007, a pediatric-based protocol, DFCI (Dana Farber Cancer Institute), was used as the standard regimen for all patients (n = 32). The two groups (DFCI and non-DFCI) had comparable baseline characteristics. Complete response rates were not significantly different between the DFCI- and non-DFCI-treated groups. The 3-year relapse free survival (RFS) and overall survival (OS) were significantly higher in the DFCI-treated group (p < 0.0001 and p = 0.0003, respectively). On multivariate analysis, the treatment group (DFCI vs. non-DFCI) was the major prognostic factor influencing both RFS and OS. The results provide evidence supporting the superior efficacy of asparaginase-intensive pediatric-based regimens for adults with T-ALL.