Carnitine is very safe substance, and it is used not only as pharmaceutical drug but also as supplemental nutrition so that the daily intake amount is established. There are also several risk assessment about safety of carnitine. Safety studies for pharmaceutical carnitine in animal showed no safety issues. Carnitine is metabolized trimethylamine (TMA) and then it is converted into trimethylamine-N-oxide (TMAO) by flavin-containing monooxygenase form 3 (FMO3) in liver. It is very rare but patients who have mutation in FMO3 exhale TMA causing fish odor syndrome. In 2013, an article was published claiming the hypothesis that “TMAO is a causative compound of atherosclerosis.” The hypothesis intrigued many researchers because it pointed out the relationship between intestinal microbiota and atherosclerosis. However, there are many refuting articles in animal experiments and clinical studies for this hypothesis and causes a lot of controversy regarding carnitine’s merits and demerits which continues even now. Details of pros and cons of safety of carnitine are described in this chapter.