Human anthrax cases reported in the country of Georgia increased 75% from 2011 (n = 81) to 2012 (n = 142). This increase prompted a case-control investigation using 67 culture- or PCR-confirmed cases and 134 controls matched by residence and gender to investigate risk factor(s) for infection during the month before case onset. Independent predictors most strongly associated with disease in the multivariable modelling were slaughtering animals [odds ratio (OR) 7·3, 95% confidence interval (CI) 2·9–18·1, P < 0·001] and disposing of dead animals (OR 13·6, 95% CI 1·5–119·8, P = 0·02). Participants owning or working with livestock (n = 131) were additionally interviewed about livestock management practices during the previous 6 months: 53 (44%) of 121 respondents vaccinated livestock against anthrax; 19 (16%) of 116 moved livestock >1 km; 15 (12%) of 125 had sick livestock; and 11 (9%) of 128 respondents reported finding dead livestock. We recommend joint public health and veterinary anthrax case investigations to identify areas of increased risk for livestock anthrax outbreaks, annual anthrax vaccination of livestock in those areas, and public awareness education.