Historically, non-combat injuries and illnesses have had a significant impact on military missions. We conducted an anonymous cross-sectional survey to assess the prevalence and impact of common ailments among U.S. military personnel deployed to Iraq or Afghanistan during 2003-2004. Among 15,459 persons surveyed, diarrhea (76.8% in Iraq and 54.4% in Afghanistan), respiratory illness (69.1%), non-combat injuries (34.7%), and leishmaniasis (2.1%) were commonly reported. For all causes, 25.2% reported that they required intravenous fluids, 10.4% required hospitalization, and 5.2% required medical evacuation. Among ground units, 12.7% reported that they missed a patrol because of illness, and among air units, 11.7% were grounded because of illness. The incidence of diarrhea and respiratory infections doubled from the pre-combat to combat phases, and the perceived adverse impact of these illnesses on the unit increased significantly during the combat phase. Despite technologic advances in warfare and preventive medicine, illness and non-combat injuries have been common during operations in Iraq and Afghanistan, resulting in frequent transient decreases in operational efficiency.