Background: Cardiac magnetic resonance perfusion studies with adenosine stress have shown that splenic response can identify patients with inadequate pharmacologic stress. We investigate the incremental prognostic impact of splenic response ratio (SRR) in patients with normal Rubidium (Rb)-82 PET myocardial perfusion imaging (MPI). Methods: Consecutive patients undergoing dipyridamole Rb-82 PET MPI for the evaluation of coronary artery disease were screened. Spleen and liver Rb-82 activity was measured and the SRR was calculated: SRR = (Spleen stress/Liver stress)/(Spleen rest/Liver rest). Major adverse cardiac events (MACE) were determined at 1 year of follow-up in patients with normal summed stress score and normal summed difference score. Results: Of the 839 patients screened, the spleen was visualized in 703 (84%) of scans. There was significantly higher MACE observed in splenic non-responders vs splenic responders in both the normal SSS (7.8% vs 2.9%, P = .027) and the normal SDS groups (7.4% vs 2.2%, P = .014). In multivariate analysis in patients with normal SDS, splenic response was a significant, independent predictor of MACE (HR 2.97, 95% CI 1.10 to 8.04, P = .033). Conclusions: SRR is a novel imaging metric to identify patients with sub-maximal vasodilator stress and an incremental prognostic marker in patients with normal SDS and SSS (Clinical Trial Registration: https://clinicaltrials.gov/ct2/show/NCT01128023).