The aim of this study is to evaluate the possible intraoperative advantages of Nd:YAG laser and quantic molecular resonance (QMR) scalpel in oral soft tissue surgery. One hundred sixty-three interventions were evaluated. Group 1 (G1) included 77 interventions performed with Nd:YAG laser, group 2 (G2) 45 with QMR scalpel, and group 3 (G3) 41 with cold blade. Parameters analyzed were as follows: speed of incision, time of intervention, intraoperative bleeding, number of stitches, patient compliance, and operator comfort. Data were analyzed using software STATA 12 (StataCorp LP, College Station, TX, USA). Mean speed of incision was 0.54 mm/s in G1, 2.83 mm/s in G2, and 1.58 mm/s in G3, Nd:YAG laser being the slowest. However, no significant differences among times of intervention were found. In particular, interventions in G1 (221.15 ± 220.89 s) have a mean duration lower than G2 (280.56 ± 248.31 s) and G3 (316.10 ± 248.69 s). Intraoperative bleeding occurred in 29.9 % (n = 23/77) of interventions in G1, 97.8 % (n = 44/45) in G2, and 97.6 % (n = 40/41) in G3 (p < 0.0001). Mean number of stitches in G1 was statistically lower (G1, 0.10; G2, 2.07; G3, 2.29; p < 0.0001). No differences with regard to patient compliance were detected. Operator comfort was higher in G1 (p < 0.0003). Nd:YAG laser and QMR scalpel give several advantages in oral mucosal surgery: Nd:YAG laser cuts tissue slowly, but it provides a good visibility and excellent hemostasis. QMR scalpel allows a very rapid cutting with no considerable temperature increase, but there is major risk of bleeding and need for sutures with lower operator comfort.