Abstract Background context Information on short- and especially long-term mortality among patients with infectious spondylodiscitis is sparse. Purpose To analyze mortality, factors associated with death, and cause-specific mortality rates among patients with infectious nonpostoperative spondylodiscitis. Study design A case-cohort study. Patient sample We identified all patients aged 18 years or older treated for infectious spondylodiscitis from January 1994 to May 2009 at hospitals in Funen County, Denmark. Outcome measures Overall and cause-specific mortality. Methods Mortality rates among patients were compared with rates among a reference population using Kaplan-Meier plots and mortality rate ratios (MRRs). Short-term mortality was defined as deaths within first year after admission and long-term mortality was deaths thereafter. Factors associated with death were determined. Results Among 298 identified patients, 61 (20%) died within the first year. Adjusted MRRs were 16.8 (95% confidence interval: 9.9–28.5) for 0 to 90 days; 4.2 (2.5–7.0) for 91 to 365 days; 2.2 (1.6–2.9) for 1 to 4 years; and 1.7 (1.2–2.5) for 5 to 14 years. Mortality rate ratios stratified on microbiological etiology were 8.8 (3.3–22.1) for 0 to 90 days; 1.4 (0.3–5.8) for 91 to 365 days; 3.2 (2.0–5.1) for 1 to 4 years; and 1.1 (0.5–2.4) for 5 to 14 years for unknown etiology and 24.0 (13.0–44.2) for 0 to 90 days; 6.0 (3.1–11.5) for 91 to 365 days; 1.9 (1.1–3.2) for 1 to 4 years; and 2.7 (1.5–4.7) for 5 to 14 years among Staphylococcus aureus infections. The main factors associated with short-term mortality were severe neurologic deficits at the time of admission, epidural abscess, and comorbidities. Long-term mortality seemed independent of microbiological etiology. Conclusions Mortality remained high the first year after admission and thereafter decreased with time to a level close to the reference population. Short-term mortality was especially related to infection with abscess formation and neurologic deficits and long-term mortality was related to alcohol dependency.