To determine the factors that have an adverse effect on the long-term health-related quality of life (HRQOL) of veterans who have lost their extremities on the battlefield. Cross-sectional study. Tertiary prosthesis center. One hundred forty-one male Iranian veterans who have sustained unilateral lower extremity amputation during the Iran-Iraq War (1980-1988) were evaluated after an average of 21.6 years (range, 20-27 years) after amputation. No intervention. Physical and mental HRQOL according to the Short Form-36 (SF-36) Health Survey. A cutoff point to define poor versus good HRQOL was calculated using the first quartile of SF-36 physical and mental component scores. Poor physical HRQOL was positively associated with transfemoral amputation, phantom movement, low back pain, and a lower Barthel Index [odds ratios (ORs): 4.1, 7.8, 9.1, and 0.9, respectively). Poor mental HRQOL was associated with education level lower than high school diploma and the articular pain of the sound leg (OR = 2.9 and 6.5, respectively). Being employed or receiving disability was a factor that had a lower OR to associate with poor mental HRQOL (OR = 0.2). Alleviation of complaints such as low back pain and articular pain of the sound leg through appropriate medical management, granting facilities for continuing education, and employment are issues that should be considered by authorities and rehabilitative centers to increase HRQOL in amputee veterans.