The purpose of this study was to compare a maintenance-free chemotherapy protocol based on CHOP (H from hydroxydaunorubicin = doxorubicin, O from Oncovin = vincristine) to a similar protocol with a maintenance phase for the treatment of canine lymphoma. Fifty-three dogs with multicentric lymphoma were treated with a 6-month modified version of the University of Wisconsin (UW)-Madison chemotherapy protocol (UW-25). Disease-free interval (DFI) and survival were compared to a historical control group of 55 dogs treated with a similar protocol with a prolonged maintenance phase. Remission rate for the study dogs was 94.2% (complete remission = 92.3%, partial remission = 1.9%). DFI and survival between the 2 groups did not differ significantly, with median DFI and survival of the study dogs equal to 282 and 397 days compared to 220 and 303 days for the control dogs (P = .2835 and .3365, respectively). Univariate analysis identified substage b (P = .0087), German Shepherd breed (P = .0199), and body weight > 18 kg (P = .0016) as significant for worse survival. Longer survival was associated with thrombocytopenia (P = .0436). Multivariate analysis revealed that substage (P = .0388) and weight (P = .0125) retained significance for DFI, whereas substage (P = .0093), thrombocytopenia (P = .0150), and weight (P = 0 .0050) retained significance for survival. Overall, the protocol was well tolerated by the dogs, with 41.5% (22/53) requiring a treatment delay or dose modification, but only 9.4% (5/53) needing hospitalization. The 6-month chemotherapy protocol based on CHOP with no maintenance phase provides similar DFI and survival times when compared to a similar protocol with a prolonged maintenance phase.