The US Public Health Service (PHS) published new recommendations for preventing HIV seroconversion in health care workers suffering needle-stick injuries. In response, health care institutions across the United States are updating their internal protocols to meet the currently accepted standard of care in this area. We found the new guidelines lacking in critical definitions necessary to clarify practical applications in specific cases. We also found the recommendations of when to use one, two, or three drugs for post-exposure prophylaxis confusing. We report our university hospital's experience with needle-stick injuries over the past year. We propose modified guidelines that more finely stratify risk categories, define clinical variables which occur in practice, and simplify the algorithm for case management. The cost of managing our cases according to the modified guidelines are compared with management costs using the PHS guidelines. Potential costs of applying the PHS guidelines in our institution ranged from $68,994-$260,544; according to our modified guidelines, costs would range from $19,199-$54,749. We also present an analysis of the number of injured health care workers who need to be treated to prevent one case of seroconversion in the various risk stratifications.