The occurrence of a massive waterborne outbreak of Cryptosporidium infection in Milwaukee, Wisconsin provided an opportunity to evaluate the effectiveness of point-of-use home water filters in preventing diarrheal illness associated with Cryptosporidium infection. Of 155 filter owners who responded to a televised request to contact the City of Milwaukee Health Department, 99 (64%) completed a self-administered questionnaire regarding their sources of drinking water, the characteristics of their home water filters, and diarrheal illness during the outbreak. Diarrhea among respondents was independently associated with residence in southern or central Milwaukee (the area served by the implicated South water treatment plant), having a home water filter with a pore diameter of greater than 1 micron, and drinking unfiltered tap water in a public building in southern Milwaukee. Among residents of southern and central Milwaukee, two (18%) of 11 persons who drank only submicron-filtered water at home and who did not drink unfiltered South plant water at work had watery diarrhea, compared with 50% (n = 2), 63% (n = 35), and 80% (n = 15) who reported drinking South plant water that was unfiltered or passed through a filter with a pore diameter > 1 micron at work only, home only, or both home and work, respectively (P = 0.02). The data indicate that use of submicron point-of-use water filters may reduce risk of waterborne cryptosporidiosis.