This retrospective study aimed to evaluate the clinical characteristics and prognostic factors of Asian patients with primary mediastinal large B-cell lymphoma (PMBCL) and to determine the role of rituximab in this entity. Forty-one consecutive patients from 1997 to 2009 were included: 14 received CHOP chemotherapy (cyclophosphamide, doxorubicin, vincristine, prednisolone), while 27 more recently treated patients received CHOP with rituximab (R-CHOP). All patients with a complete or partial response received consolidation involved field radiotherapy (RT). After a median follow-up of 31.2 months (104.4 months for CHOP and 28.8 months for R-CHOP), the overall survival (OS) and progression-free survival (PFS) for R-CHOP- and CHOP-treated patients were 87% vs. 57% and 88% vs. 36%, respectively. R-CHOP resulted in an improvement of PFS (hazard ratio [HR] 8.27, 95% confidence interval [CI] 2.23-30.74, p = 0.002) and OS (HR 4.20, 95% CI 1.05-16.8, p = 0.04). Nineteen patients had positron emission tomography/computed tomography (PET/CT) evaluation after six cycles of R-CHOP (metabolic complete response 13, partial metabolic response five, and metabolic progression one). All five patients with a metabolic partial response received RT instead of intensive salvage chemotherapy; four remained progression-free. In patients with PMBCL, R-CHOP in combination with involved field radiotherapy portended a 3-year OS rate of 87%, which is comparable to historical survival rates with more intensive chemotherapy regimens.