Falls, gait variability and increased energy cost of walking are common in people with multiple sclerosis (PwMS). However, no studies have as yet examined this triple association in PwMS or in other neurological populations.Does a relationship exist between gait variability, falls and the energy cost of gait in PwMS?This cross sectional study included 88 PwMS (50 women), mean age 39.8 (S.D = 13.0) and mean disease duration of 6.2 (SD = 8.2) years since diagnosis. Energy expenditure during walking was collected via a portable metabolic device (COSMED K5, COSMED Srl, Roma, Italy). Gait variability was measured by an electronic walkway (GAITRite™). Participants were divided into groups based on fall history (fallers and non-fallers). Differences between groups in terms of energy expenditure measures and gait variability metrics were determined by the analysis of variance test. The relationship between gait variability and energy cost of walking was examined by the Pearson's correlation coefficient test.Thirty-three PwMS were classified as fallers and 55 as non-fallers. Non-significant differences between groups were observed in the energy expenditure measures, including cost of walking. Fallers demonstrated higher step length variability compared with non-fallers (4.58 (S.D. = 2.42 vs. 3.40 (S.D. = 1.40); p-value = 0.005). According to the Pearson's correlation coefficient analysis, a significant relationship was found between step length variability and energy cost of walking in the non-fallers group (Rho = 0.372, P-value = 0.006) and the total group (Rho = 0.296, p-value = 0.005), but not in those PwMS with a history of falls.We demonstrated a significant relationship between increased gait variability and energy expenditure while walking only in MS patients without a history of falls. This is important as there is evidence of the clinical relevance of increased gait variability, poor fitness level and high risk of falling in the MS population.