Background: Evidence is growing on anticancer effects of statins. We investigated whether the effectiveness of treatment with statins after ischemic stroke on mortality is influenced by a history of cancer. Methods: Analyses of 90-day survivors of ischemic stroke (2012–2016; 45 hospitals) using linked registry and administrative data. Dispense of statins within 90 days postdischarge was determined from pharmaceutical records. Participants were followed from 91 days postdischarge until death or June 30, 2018. History of cancer was determined from hospital data. Propensity score–adjusted Cox proportional hazards regression model was used to determine the association between being dispensed statins and survival. The influence of history of cancer on this association was assessed based on the concepts of (1) statistical interaction and (2) biological interaction using 3 indices: relative excess risk due to interaction>0, attributable proportion due to interaction >0, or synergy index >1. Results: Among 9948 eligible participants (median age=72 years, 42% female), there were 1463 deaths. In adjusted analyses, there was no statistical interaction between being dispensed statins and history of cancer on mortality ( P =0.156). However, being dispensed statins had a significant positive biological interaction with having a history of cancer on mortality: relative excess risk due to interaction, 2.80 (95% CI, 1.56–5.05), attributable proportion due to interaction, 0.45 (95% CI, 0.23–0.66), and synergy index, 2.14 (95% CI, 1.32–3.49). Conclusions: Treatment with statins after ischemic stroke may confer additional survival benefits for people who also have had cancer.