Abstract Background Rabacfosadine (RAB, Tanovea‐CA1) is a novel chemotherapy agent conditionally approved for the treatment of lymphoma in dogs. Hypothesis/Objectives To determine the efficacy and safety of RAB in dogs with lymphoma. Animals One hundred and fifty‐eight client‐owned dogs with naïve or relapsed multicentric lymphoma were prospectively enrolled from January to October 2019. Methods Dogs were randomized to receive RAB or placebo at a 3 : 1 ratio. Treatment was given every 21 days for up to 5 treatments. Study endpoints included progression‐free survival (PFS), overall response rate (ORR) at a given visit, best overall response rate (BORR), and percent progression free 1 month after treatment completion. Safety data were also collected. Results The median PFS was significantly longer in the RAB group compared to placebo (82 vs 21 days; P