Patients with ALS may have insufficientenergy substrates, due to dysphagia and hypermetabolism, which adversely affects the prognosis. Hyperlipidaemia has been reported to be associated with ALS and to represent a significant prognostic factor for survival in ALS. The aim of this study was to examine the prevalence of dyslipidaemia among a cohort of patients with ALS and how the lipid profile of patients with ALS influenced the prognosis. This was a prospective observational cohort study comprising 512 ALS patients, recruited for the TRO19622 (Olesoxime) investigational medicinal product trial. Fasting serum concentrations of total cholesterol (TC), low density lipoprotein cholesterol (LDL-C) and high density lipoprotein cholesterol (HDL-C) were measured as part of routine monitoring in the trial. Seventy-three percent of the participants had hypercholesterolaemia (defined as total cholesterol ≥ 5.1 mmol/l) at the screening visit. The prevalence of hypercholesterolaemia decreased with time and was 64% at 18 months follow-up. On unadjusted analysis total cholesterol, LDL-C and LDL/HDL ratio had a statistically significant effect on survival (p = 0.015, 0.003 and 0.027, respectively). When adjusted for prognostic covariates, however, none of the lipid measures was found to have a statistically significant effect on survival. In conclusion, prognosis in ALS is not influenced by the lipid profile of patients.