The present study aimed to investigate the prognostic importance of the neutrophil-to-lymphocyte ratio (NLR) in patients with amyotrophic lateral sclerosis (ALS). Among 322 patients diagnosed as having definite, probable, or possible ALS at a single tertiary hospital, 194 patients were included in the final analysis. Patients were divided into three groups (T1, T2, and T3) according to the tertile of their NLR. Survival rate was significantly lower in T3 compared to the other groups (log-rank test; T1 vs. T3, p = 0.009; T2 vs. T3, p = 0.008). Median survival duration was 37.0 (24.0–56.0), 32.5 (19.5–51.2), and 22.0 (17.0–38.0) months in T1, T2, and T3, respectively. In a multivariable Cox proportional hazards regression analysis, the hazard ratio of age at onset, bulbar-onset, and NLR (T3/T1) was 1.04 (1.02–1.06, p < 0.001), 1.68 (1.10–2.57, p = 0.015), and 1.60 (1.01–2.51, p = 0.041), respectively. A high baseline NLR may serve as a useful indicator for short survival duration in patients with ALS.