Our objective was to examine occupational risk factors for musculoskeletal disorders of the neck, back, and knee among railroad maintenance-of-way (MOW) workers. Four thousand eight-hundred sixteen active, retired, and disabled members of the Brotherhood of Maintenance of Way Employes Division (BMWED) completed a survey. We computed adjusted prevalence ratios (aPRs) using Poisson regression for neck, back, and knee musculoskeletal symptoms by work exposures, adjusted for age, region, race/ethnicity, smoking, and potential second job and spare time vehicle vibration exposure. Among active male BMWED members, we found associations between use of high-vibration vehicles and neck pain (aPR = 1.47, 95% confidence interval (CI): 1.07-2.03) and knee pain (aPR = 1.38, 95% CI: 1.04-1.82) for more than 1.9 years (vs 0) of full-time equivalent use; but not back pain. Back pain radiating below the knee (sciatica indicator) was associated with high-vibration vehicle use greater than 0.4 and less than 1.9 years (aPR = 1.58, 95% CI: 1.15-2.18). We also found significant associations between often or always lifting, pushing, pulling, or bending on the job (vs seldom or never) and neck pain (aPR = 2.43, 95% CI: 1.20-4.90), back pain (aPR = 1.94, 95% CI: 1.24-3.03), the sciatica indicator (aPR = 5.18, 95% CI: 1.28-20.95), and knee pain (aPR = 2.84, 95% CI: 1.47-5.51), along with positive gradients in the outcome by exposure time. Biomechanical work exposures, including force and nonneutral postures, were associated with neck, lower back, and knee pain. Whole-body vibration, as measured by the duration of use of high-vibration vehicles, was associated with neck pain, knee pain, and sciatica. Prevention programs should address occupational risk factors for musculoskeletal disorders among MOW workers.