L-Carnitine is an endogenous compound thought to be helpful in treating patients with dialysis-related hypotension and muscle cramps; however, sufficient evidence for these indications is lacking. Systematic review and meta-analysis. Adult patients with end-stage renal disease receiving long-term hemodialysis. All published English-language reports of randomized placebo-controlled trials of L-carnitine supplementation in adult long-term hemodialysis patients. Supplemental L-carnitine (or placebo) for at least 8 weeks. Random-effects pooled odds ratio for intradialytic cramping or hypotension in L-carnitine-treated participants. Of 317 potentially relevant articles, 7 (total enrollment of 193 patients) met criteria for inclusion. Four articles reported results for both hypotension and cramps, 1 had results for only hypotension, and 2 reported results for only cramps. Using data from all 6 relevant trials, the pooled odds ratio for cramping after L-carnitine supplementation was 0.30 (95% confidence interval, 0.09 to 1.00; P = 0.05). Analysis of the 5 studies examining the response of intradialytic hypotension to l-carnitine supplementation yielded a pooled odds ratio of 0.28 (95% confidence interval, 0.04 to 2.23; P = 0.2). The small number of available studies yielded limited statistical power. In addition, there was considerable interstudy heterogeneity. Although suggestive in the case of muscle cramping, the available evidence does not confirm a beneficial effect of L-carnitine supplementation on dialysis-related muscle cramping or intradialytic hypotension. Additional study in the form of large rigorous randomized trials is needed in both cases.