Sustainable Development Goal (SDG) Indicator 6.2.1 requires household handwashing facilities to have soap and water, but there are no guidelines for handwashing water quality. In contrast, drinking water quality guidelines are defined: water must be "free from contamination" to be defined as "safely managed" (SDG Indicator 6.1.1). We modeled the hypothesized mechanism of infection due to contaminated handwashing water to inform risk-based guidelines for microbial quality of handwashing water. We defined two scenarios that should not occur: (1) if handwashing caused fecal contamination, indicated using Escherichia coli, on a person's hands to increase rather than decrease and (2) if hand-to-mouth contacts following handwashing caused an infection risk greater than an acceptable threshold. We found water containing <1000 E. soli colony-forming units (CFU) per 100 mL removes E. coli from hands with>99.9% probability. However, for the annual probability of infection to be <1:1000, handwashing water must contain <2 x 10(-6) focus-forming units of rotavirus, <1 x 10(-4) CFU of Vibrio cholerae, and <9 x 10(-6) Cryptosporidium oocysts per 100 mL. Our model suggests that handwashing with nonpotable water will generally reduce fecal contamination on hands but may be unable to lower the annual probability of infection risks from hand-to-mouth contacts below 1:1000.