INTRODUCTION: Calcium channel blocker (CCB) overdoses cause significant morbidity and mortality. Dihydropyridine CCBs cause peripheral vascular dilation and at high doses cardiac dysfunction. Amlodipine, a dihydropyridine, causes peripheral vasodilation from release of nitric oxide (NO) in addition to calcium channel blockade; NO scavenging is a potential treatment. Methylene blue (MB) inhibits NO directly and inhibits NO production. We compared the effects of MB versus norepinephrine (NE), with time to death as the primary outcome, in a porcine amlodipine toxicity model. METHODS: Animals were anesthetized and instrumented, and an amlodipine infusion was administered to mimic oral overdose. After 70 minutes, each group was resuscitated with normal saline. Animals in each group were then randomized to receive either MB or NE. Hemodynamic parameters, including mean arterial pressure and cardiac output, were recorded every 10 minutes. The primary outcome was survival time (Kaplan-Meier analysis and log-rank test). RESULTS: Interim analysis after 15 animals (7 MB, 8 NE) revealed that MB was clearly not superior to NE. Overall, 1 of 7 animals in the MB group survived to 300 minutes compared with 2 of 8 animals in the NE group. The median survival time was 100 minutes for the MB group and 177 minutes for the NE group. Survival time did not differ by group (log-rank test p = 0.29). CONCLUSION: In this porcine model of amlodipine toxicity, methylene blue did not improve survival time compared with norepinephrine. Whether methylene blue is beneficial in combatting distributive shock in amlodipine toxicity remains unclear and requires further study.