Few experimental studies have examined surgical drilling in human bone, and no studies have inquired into this aspect for a popular commercially-available artificial bone used in biomechanical studies. Sixteen fresh-frozen human femurs and five artificial femurs were obtained. Cortical specimens were mounted into a clamping system equipped with a thrust force and torque transducer. Using a CNC machine, unicortical holes were drilled in each specimen at 1000 rpm, 1250 rpm, and 1500 rpm with a 3.2 mm diameter surgical drill bit. Feed rate was 120 mm/min. Statistical significance was set at p < 0.05. Force at increasing spindle speed (1000 rpm, 1250 rpm, and 1500 rpm), respectively, showed a range for human femurs (198.4 ± 14.2 N, 180.6 ± 14.0 N, and 176.3 ± 11.2 N) and artificial femurs (87.2 ± 19.3 N, 82.2 ± 11.2 N, and 75.7 ± 8.8 N). For human femurs, force at 1000 rpm was greater than at other speeds (p ≤ 0.018). For artificial femurs, there was no speed effect on force (p ≥ 0.991). Torque at increasing spindle speed (1000 rpm, 1250 rpm, and 1500 rpm), respectively, showed a range for human femurs (186.3 ± 16.9 N·mm, 157.8 ± 16.1 N·mm, and 140.2 ± 16.4 N·mm) and artificial femurs (67.2 ± 8.4 N·mm, 61.0 ± 2.9 N·mm, and 53.3 ± 2.9 N·mm). For human femurs, torque at 1000 rpm was greater than at other speeds (p < 0.001). For artificial femurs, there was no difference in torque for 1000 rpm versus higher speeds (p ≥ 0.228), and there was only a borderline difference between the higher speeds (p = 0.046). Concerning human versus artificial femurs, their behavior was different at every speed (force, p ≤ 0.001; torque, p < 0.001). For human specimens at 1500 rpm, force and torque were linearly correlated with standardized bone mineral density (sBMD) and the T-score used to clinically categorize bone quality (R ≥ 0.56), but there was poor correlation with age at all speeds (R ≤ 0.37). These artificial bones fail to replicate force and torque in human cortical bone during surgical drilling. To date, this is the largest series of human long bones biomechanically tested for surgical drilling.