Abstract The objective of this experimental animal study was to compare the surgical precision of a flexible CO2 laser fiber with that of monopolar electrosurgery in porcine myometrium. The subjects were 6 live adult non-pregnant female pigs. Linear injury to the uterine horns was created using a flexible CO2 laser fiber at 5W, 10W, and 15W and with monopolar electrosurgery at 10W, 20W, 30W, and 40W in both cut and coagulation modes. Hysterectomy was then performed in the live animals. Cross-sections of the tissue were processed and stained using Masson trichrome to differentiate damaged from undamaged myometrium. Measurement means were compared using analysis of variance with Tukey honest significant difference correction; p <.05 indicated significance. Incision width of the laser at 5W and 10W was significantly less than both monopolar coagulation at all power settings and monopolar cut at 30W and 40W (all p <.01), at 5W was also significantly less than monopolar cut at 10W (p = .03), and at 15W was significantly less than monopolar coagulation at 40W (p = .001). Incision depth of the laser at 5W was significantly less than monopolar coagulation at 40W and laser at 15W (both p = .01), at 15W was significantly greater than monopolar coagulation at 10W and monopolar cut at 10, 20, and 30W (p ≤.01), and increased proportional to power for all 3 energy types. Collateral thermal damage width at all laser power settings was significantly less than at all monopolar coagulation power settings (p ≤.04) with the exception of the laser at 15W compared with monopolar coagulation at 10W (p = .30), and at all laser power settings was significantly less than at all monopolar coagulation power settings (p <.001). Collateral thermal damage depth of the laser at 5W and 10W was significantly less than monopolar cut at 30W (p ≤.002) and increased proportional to power in monopolar coagulation mode but remained constant with the laser. Incising efficiency of the laser at 5W was significantly greater than monopolar coagulation at 10W (p = .04), at 10W was significantly greater than at all monopolar power settings (p ≤.007) except cut at 40W (p = .29), and at 15W was significantly greater than that of every other energy type and power setting tested (p ≤.04). These findings support the hypothesis that CO2 laser energy delivered via a flexible fiber system would exhibit greater surgical precision than monopolar electrosurgery, in both cut and coagulation modes, as defined by 3 parameters: incising efficiency, changes in incision depth compared with width as power increases, and variability in the resulting incision measurements. Because increased thermal damage has been associated with delayed tissue necrosis and adhesion formation, these findings prompt the design of a comparative survival animal study to assess additional clinically relevant parameters.