The regimen of cyclophosphamide, doxorubicin, vincristine, and prednisolone, known as CHOP therapy, has been established as the standard treatment for aggressive non-Hodgkin's lymphoma (NHL). Although patients categorized as low (L) and low-intermediate (L-I) risk using the International Prognostic Index have favorable prognoses in Western countries, the efficacy and safety of CHOP therapy has not been prospectively evaluated in Japan. We conducted a phase II study of CHOP in L and L-I risk Japanese patients, evaluating overall survival (OS) as the primary endpoint. A total of 213 patients were enrolled and treated with eight courses of CHOP. Efficacy was evaluated in 168 eligible patients (L risk, 87; L-I risk, 81). Five-year OS rates in all eligible, L, and L-I risk patients were 68 % [95 % confidence interval (CI): 61-76 %], 73 % (95 % CI: 63-82 %), and 64 % (95 % CI: 53-74 %), respectively. The major toxicity observed was grade 4 neutropenia (64 %). Grade 4 non-hematological toxicities were observed as follows: one case each of paralytic ileus, convulsions, hypoxemia due to interstitial pneumonia, and reactivated fulminant hepatitis B. These results show reasonable efficacy and safety of the CHOP regimen in Japanese patients with lower risk aggressive NHL (UMIN-CTR Number C000000053).