Context: Excessive cardiac long-chain fatty acid (LCFA) metabolism/storage causes cardiomyopathy in animal models of type 2 diabetes. Medium-chain fatty acids (MCFAs) are absorbed and oxidized efficiently. Data in animal models of diabetes suggest MCFAs may benefit the heart. Objective: Our objective was to test the effects of an MCFA-rich diet vs an LCFA-rich diet on plasma lipids, cardiac steatosis, and function in patients with type 2 diabetes. Design: This was a double-blind, randomized, 2-week matched-feeDing study. Setting: The study included ambulatory patients in the general community. Patients: Sixteen patients, ages 37-65 years, with type 2 diabetes, an ejection fraction greater than 45%, and no other systemic disease were included. Intervention: Fourteen days of a diet rich in MCFAs or LCFAs, containing 38% as fat in total, was undertaken. Main Outcome Measures: Cardiac steatosis and function were the main outcome measures, with lipidomic changes considered a secondary outcome. Results: The relatively load-independent measure of cardiac contractility, S, improved in theMCFA group (P < .05). Weight-adjusted stroke volume and cardiac output decreased in the LCFA group (both P.05). The MCFA, but not the LCFA, diet decreased several plasma sphingolipids, ceramide, and acylcarnitines implicated in diabetic cardiomyopathy, and changes in several sphingolipids correlated with improved fasting insulins. Conclusions: Although a diet high inMCFAsdoes not change cardiac steatosis, our findings suggest that the MCFA-rich diet alters the plasma lipidome and may benefit or at least not harm cardiac function and fasting insulin levels in humans with type 2 diabetes. Larger, long-term studies are needed to further evaluate these effects in less-controlled settings.