Blood exposure rates among home care and hospice nurses (RNs) in the United States are markedly lower for nurses with more home care/hospice experience, whether or not they have more total years of nursing experience (i.e., in other work environments). This study examined whether the protective effect of home care/hospice experience was greater for nurses who worked under three types of circumstances that are typical of the home care/hospice work environment and conducive to blood exposure. A mail survey was conducted in 2006 among home care/hospice nurses in North Carolina, a largely rural state in the southeastern U.S. The adjusted response rate was 69% (n=833). Blood exposure rates were higher among nurses with ≤5 years' experience in home care/ hospice. Contrary to expectations, the protective effect of more experience was greater among nurses who did not have limited access to safety devices/personal protective equipment, did not have to rush during home visits, and did not often visit homes with unrestrained pets, unruly children, poor lighting, or extreme clutter. These results suggest that characteristics of the home care/hospice work environment limit nurses' ability to use their experience to prevent blood exposure.