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Background The surgical approaches of colloid cysts commonly include endoscopy or open microsurgery. Each approach carries its own challenges, feasibility, and complications. The aim of the current study is to compare endoscopic versus open microsurgical excision of third ventricular colloid cysts. Methods A retrospective cohort study was conducted to compare the surgical outcomes of endoscopic versus open microsurgical (transcortical-transventricular and transcallosal approaches) excision of colloid cyst of the third ventricle at a tertiary-care medical institute. All patients with a neuroradiologic diagnosis of colloid cyst who subsequently underwent surgical management between January 2003 and June 2020 were included. The neurologic outcome was assessed at the last follow-up visit. Results A total of 32 patients with colloid cysts were included in the study. The mean age was 35.8 ± 18.3 years (range, 4–75 years). Female patients slightly outnumbered male patients (n = 17; 53.1%). A total of 21 patients (65.6%) underwent endoscopic resection of the colloid cyst. Complications were encountered in 7 patients (endoscopic, n = 3; microsurgery, n = 4; P = 0.151). Recurrence was identified in 4 patients (endoscopic, n = 3; microsurgery, n = 1; P = 0.673). Most patients improved neurologically on follow-up visits to the clinic (endoscopic, n = 19; microsurgery, n = 9; P = 0.482). Conclusions Both endoscopic and microsurgical approaches provide favorable surgical outcomes in colloid cyst resection. The complication rates between both approaches is statistically insignificant. The optimal surgical approach for colloid cyst resection remains controversial.