In a prospective observational study of 40 nurses (20 with diagnosed hand irritation and 20 without), nurses with damaged hands did not have higher microbial counts (P = .63), but did have a greater number of colonizing species (means: 3.35 and 2.63, P = .03). Although numbers were small, nurses with damaged hands were significantly more likely to be colonized with Staphylococcus hominis (P = .03). Fifty-nine percent of S hominis isolates from nurses with damaged hands were resistant to methicillin compared with 27% of isolates from those with healthy skin (P = .14). Twenty percent of nurses with damaged hands were colonized with Staphylococcus aureus compared with none of the nurses with normal hands (P = .11). Nurses with damaged hands were also twice as likely to have gram-negative bacteria (P = .20), entercocci (P = .13), and Candida (P = .30) present on the hands. Antimicrobial resistance of the coagulase-negative staphylococcal flora (with the exception of S hominis) did not differ between the 2 groups, nor did a trend toward increasing resistance exist when compared with other studies during the past decade. Skin moisturizers and protectant products were used almost universally by nurses at work, primarily products brought from home. Efforts to improve hand condition are warranted because skin damage can change microbial flora. Such efforts should include assessment or monitoring of hand care practices, formal institutional policy adoption and control of use of skin protectant products or lotions, and prudent use of latex gloves or more widespread use of powder-free and nonlatex products.