Background: Despite advances in antithrombotic therapies and invasive technology, the risk of recurrent ischemic complications in patients with non-ST-elevation acute coronary syndromes(NSTE-ACSs) remains substantial. Ranolazine is a novel agent that inhibits the late sodium current thereby reducing cellular sodium and calcium overload and has been shown to reduce ischemia in patients with chronic stable angina. Study Design: MERLIN-TIMI 36 is a phase III, randomized, double-blind, parallel-group, placebo-controlled, multinational clinical trial to evaluate the efficacy and safety of ranolazine during long-term treatment of patients with NSTE-ACS receiving standard therapy(N=6500). Eligible patients are randomized 1 ∶1 to ranolazine or matched placebo, initiated as 200 mg intravenously over 1 hour, followed by an 80-mg/h infusion(40 mg/h for patients with severe renal insufficiency) for up to 96 hours and oral ranolazine ER 1000 mg BID or matched placebo until the end of study. The primary end point is the time to first occurrence of any element of the composite of cardiovascular death, myocardial infarction, or recurrent ischemia. Secondary end points include ischemia on Holter monitoring, hospitalization for new or worsening heart failure, quality of life measures, and exercise performance. The evaluation of longterm safety will include death from any cause and symptomatic documented arrhythmia. Recruitment began in October 2004. The trial will continue until 730 major cardiovascular events and 310 deaths are recorded with expected completion in 24 to 28 months. Conclusions: MERLIN-TIMI 36 will evaluate the role of ranolazine in the acute and chronic management of patients presenting with NSTE-ACS. Background: Despite advances in antithrombotic therapies and invasive technology, the risk of recurrent ischemic complications in patients with non-ST-elevation acute coronary syndromes (NSTE-ACSs) remains substantial. Ranolazine is a novel agent that inhibits the late sodium current thereby reducing cellular sodium and calcium overload and has been shown to reduce ischemia in patients with chronic stable angina. Study Design: MERLIN-TIMI 36 is a phase III, randomized, double-blind, parallel-group, placebo-controlled, multinational clinical trial to evaluate the efficacy and safety of ranolazine during long-term treatment of patients with NSTE-ACS receiving standard therapy (N = 6500). Eligible patients are randomized 1: 1 to ranolazine or matched placebo, initiated as 200 mg intravenously over 1 hour, followed by an 80-mg / h infusion (40 mg / h for patients with severe renal insufficiency) for up to 96 hours and oral ranolazine ER 1000 mg BID or matched placebo until the end of study. The p rimary end point is the time to first occurrence of any element of the composite of cardiovascular death, myocardial infarction, or recurrent ischemia. Secondary end points include ischemia on Holter monitoring, hospitalization for new or worsening heart failure, quality of life measures, and exercise performance. The evaluation of longterm safety will include death from any cause and symptomatic documented arrhythmia. Recruitment began in October 2004. The trial will continue until 730 major cardiovascular events and 310 deaths were recorded with expected completion in 24 to 28 months. Conclusions: MERLIN -TIMI 36 will evaluate the role of ranolazine in the acute and chronic management of patients presenting with NSTE-ACS.