Extensive testing of the SCC-DFTB method has been performed, permitting direct comparison to data available for NDDO-based semiempirical methods. For 34 diverse isomerizations of neutral molecules containing the elements C, H, N, and O, the mean absolute errors (MAE) for the enthalpy changes are 2.7, 3.2, 5.0, 5.1, and 7.2 kcal/mol from PDDG/PM3, B3LYP/6-31G(d), PM3, SCC-DFTB, and AM1, respectively. A more comprehensive test was then performed by computing heats of formation for 622 neutral, closed-shell H, C, N, and O-containing molecules; the MAE of 5.8 kcal/mol for SCC-DFTB is intermediate between AM1 (6.8 kcal/mol) and PM3 (4.4 kcal/mol) and significantly higher than for PDDG/PM3 (3.2 kcal/mol). Similarly, SCC-DFTB is found to be less accurate for heats of formation of ions and radicals; however, it is more accurate for conformational energetics and intermolecular interaction energies, though none of the methods perform well for hydrogen bonds with strengths under ca. 7 kcal/mol. SCC-DFTB and the NDDO methods all reproduce MP2/cc-pVTZ molecular geometries with average errors for bond lengths, bond angles, and dihedral angles of only ca. 0.01 angstrom, 1.5 degrees, and 3 degrees. Testing was also carried out for sulfur containing molecules; SCC-DFTB currently yields much less accurate heats of formation in this case than the NDDO-based methods due to the over-stabilization of molecules containing an SO bond.