Three different sequentially applied post-varicella zoster virus (VZV) exposure management strategies were employed over a 43-month period. We began by using a standard post-exposure protocol in which 50 susceptible healthcare workers (HCW) involved in hospital exposures were furloughed from work at a loss to the hospital of 424 workdays and $46,000. Of the eight nosocomial cases of VZV infection in HCWs, four (50%) caused future HCW and patient exposure. In trial I, we substituted a post-exposure screening procedure for the standard work furlough procedure. We screened 77 exposed staff resulting in one nosocomial VZV infection that was the source of another exposure incident. No secondary cases of varicella resulted from this exposure and only 20 days of furlough time were used during trial I. As VZV resulting from a home exposure source was responsible for most hospital exposures in which HCWs were the source, our trial II protocol added the Centers for Disease Control's (CDC) off-duty procedure, but limited its use to susceptibles exposed at home. The 43-month overall attack rate of nosocomial varicella was 4.7%, while the true home exposure attack rate was 79% (p < .00001). There was an average of 42.4 lost workdays charged to the hospital per incident under the standard protocol and three days per incident in the combined experience of trials I and II (p < .0001). Both trial protocol periods saved the hospital many potentially lost HCW days, 592 and 401, respectively, but the trial I protocol led to an observed increase in hospital exposure incidents. While the trial II protocol resulted in more lost workdays (120 of 521) than the trial I protocol, it prevented 18 additional HCW exposures. We conclude that the trial II protocol is safe and the most cost-effective of the three management strategies.