Context: The amino acid L-arginine is a substrate for nitric oxide synthase and is increasingly used as a health supplement. Prior studies suggest that L arginine has the potential to reduce vascular stiffness. Objective: To determine whether the addition of L-arginine to standard postinfarction therapy reduces vascular stiffness and improves ejection fraction over 6-month follow-up in patients following acute ST-segment elevation myocardial infarction. Design and Setting: Single-center, randomized, double-blind, placebo-controlled trial with enrollment from February 2002 to June 2004. Patients: A total of 153 patients following a first ST-segment elevation myocardial infarction were enrolled; 77 patients were 60 years or older. Intervention: Patients were randomly assigned to receive L-arginine(goal dose of 3 g 3 times a day) or matching placebo for 6 months. Main Outcome Measures: Change in gated blood pool-derived ejection fraction over 6 months in patients 60 years or older randomized to receive L-arginine compared with those assigned to receive placebo. Secondary outcomes included change in ejection fraction in all patients enrolled, change in noninvasive measures of vascular stiffness, and clinical events. Results: Baseline characteristics, vascular stiffness measurements, and left ventricular function were similar between participants randomized to receive placebo or L-arginine. The mean(SD) age was 60(13.6) years; of the participants, 104(68% ) were men. There was no significant change from baseline to 6 months in the vascular stiffness measurements or left ventricular ejection fraction in either of the 2 groups, including those 60 years or older and the entire study group. However, 6 participants(8.6% ) in the L-arginine group died during the 6-month study period vs none in the placebo group(P=.01). Because of the safety concerns, the data and safety monitoring committee closed enrollment. Conclusions: L-Arginine, when added to standard postinfarction therapies, does not improve vascular stiffness measurements or ejection fraction and may be associated with higher postinfarction mortality. L-Arginine should not be recommended following acute myocardial infarction. Context: The amino acid L-arginine is a substrate for nitric oxide synthase and is increasingly used as a health supplement. Objective Studies: that L arginine has a potential to reduce vascular stiffness. Objective: To determine whether the addition of L-arginine to standard postinfarction therapy due to vascular stiffness and Frankfort improvement fraction over 6-month follow-up in patients following acute ST-segment elevation myocardial infarction. Design and Setting: Single-center, randomized, double-blind, placebo-controlled trial with enrollment from Patients: A total of 153 patients were followed first a first ST-segment elevation myocardial infarction were enrolled; 77 patients were 60 years or older. Intervention: Patients were randomly assigned to receive L-arginine (goal dose of 3 g 3 times a day) or matching placebo for 6 months. Main Outcome Measures: Change in gated blood pool-derived ejection fraction over 6 months in patients 60 years or older rand omitting to receive L-arginine compared with those assigned to receive placebo. Secondary outcome included change in ejection fraction in all patients enrolled, change in noninvasive measures of vascular stiffness, and clinical events. Results: Baseline characteristics, vascular stiffness measurements, and left ventricular The mean (SD) age was 60 (13.6) years; of the participants, 104 (68%) were men. There was no significant change from baseline to 6 months in However, 6 participants (8.6%) in the L-arginine group died during the 6-month study period vs none in the placebo group (P = .01). Because of the safety concerns, the data and safety monitoring committee closed enrollment. Conclusions: L-Arginine, when added to standard postinfarction th erapies, does not improve vascular stiffness measurements or ejection fraction and may be associated with higher postinfarction mortality. L-Arginine should not be recommended following acute myocardial infarction.