The aim of this study was to compare the effectiveness of Carisolv with that of two other alkaline substances: NaOCl and Ca(OH)2. Sixty extracted teeth were randomly divided into three groups and split down the center of a carious lesion. In group I, one half of the cavity was excavated with NaOCl (0.5%, pH 11.7), the corresponding half with Ca(OH)2 (pH 12.4); in group II with NaOCl and Carisolv; and in group III with Ca(OH)2 and Carisolv (n = 20 in each case). Carisolv hand instruments were used. Histological specimens were subsequently produced from all cavities and analyzed with a light-microscope following Mallory-Azan staining. The thickness of the remaining caries was measured (< 1 mm or > 1 mm) and the locations were recorded. The data were statistically evaluated using the chi-square test. In group I, 50.5% of the specimens treated with NaOCI and 48.7% treated with Ca(OH)2 were evaluated to be caries-free. The results in group II were NaOCl 61.5% and Carisolv 75.4% caries-free, and in group III Ca(OH)2 61.2% and Carisolv 73.9%. No statistically significant differences were found between NaOCl and Ca(OH)2 excavation (group I: p = 0.89). Compared to NaOCl and Ca(OH)2, Carisolv produced significantly better results for chemo-mechanical caries removal (groups II + III: p < 0.05). In the NaOCl and Ca(OH)2 treated specimens, carious layers with a thickness >1 mm were found significantly more often than in the Carisolv-treated specimens (groups II + III: p < 0.05), whereas there were no differences between NaOCl and Ca(OH)2 excavation (p = 0.06). There were no statistically significant differences in the location of the remaining caries in any of the groups (p > 0.05).