Polyferm and Fermosorb are oral acid resistant antimicrobial enzyme preparations designed specifically for therapy/prophylaxis of intestinal infections in animal neonates. Both are authorized for use throughout the former Soviet Union, but until now only Fermosorb is being applied on a large scale. The comparative studies on these two preparations, described in this paper, were carried out in order to find differences between the preparations. Characteristics that were compared included stability of the preparations in acidic environment as well as in storage (in vitro studies), and their efficacy for the treatment and prophylaxis of colibacillosis in newborn calves (in vivo studies). Results of in vitro studies revealed that proteolytic enzymes of Polyferm (as well as lytic enzymes of Fermosorb) were suitably (and in a very similar magnitude) protected from the influence of the acidic environment. The complete enzyme activity retention period in storage at room temperature of Polyferm and Fermosorb was equally high (5 years). In vivo studies performed on 2000 calves revealed that both preparations were highly effective and, although the efficacy of Polyferm was a bit lower than that of Fermosorb (93.6% vs. 95.0%, 94.6% vs. 95.8% for therapy and prophylaxis of colibacillosis, respectively), no statistically significant differences in the number of Polyferm vs. Fermosorb cured/protected animals were found. It is concluded that there were no reasons, other than the lack of supportive advertising materials, that might impede the utility of Polyferm.