Generalized vaccinia (GV), progressive vaccinia (PV), and eczema vaccinatum (EV) are adverse reactions following smallpox vaccination. We investigated all reports suggestive of GV, PV, or EV among United States civilian smallpox vaccinees during 2003 and applied standard case definitions. We identified 29 reports of possible GV among 38,440 vaccinees; 2 (7%) of the reports met the case definition. One case of GV was confirmed by identifying vaccinia from a lesion distant from the vaccine site using polymerase chain reaction. The other case was classified as probable GV, because confirmatory testing was not done. We identified 3 potential EV cases and 7 potential PV cases, none of which met the standard case definition. GV, PV, and EV were rare or absent following smallpox vaccination after careful screening of potential vaccinees. GV may be difficult to distinguish from other rashes, and confirmatory testing is recommended. Careful prevaccination screening probably contributed to the low incidence of these adverse reactions following smallpox vaccination.