Multiple-limb loss due to war-theater injuries results in a unique group of servicemembers requiring intensive rehabilitation and diverse prosthetic devices. This article compares the Vietnam and the Operation Iraqi Freedom/Operation Enduring Freedom (OIF/OEF) groups with war-theater-associated multiple-limb loss to document significant changes in health status, prosthetic-device use, and long-term prognosis. During 2007 and 2008, a national survey queried 73 Vietnam veterans and 61 OIF/OEF servicemembers sustaining multiple-limb loss. Average years since limb loss are 39 for Vietnam veterans and 3 for OIF/OEF servicemembers. Self-rated health status was excellent or very good in 38.9% of the Vietnam group and 60.7% of the OIF/OEF group (p = 0.01). More of the OIF/OEF group than the Vietnam group reported performing high-impact aerobic activities, 18% versus 3% (p = 0.005). The OIF/OEF group currently uses more diverse prosthetic-device types than the Vietnam group. Based on Vietnam veterans' 39-year experience, the long-term prognosis for OIF/OEF servicemembers with multiple-limb loss is an active, fulfilling life. The healthcare team caring for these patients should carefully address proper prosthesis fit and maintenance of good health and function.