Objectives: The aim of the study was to describe the feasibility of open fetal microneurosurgery for intrauterine spina bifida (SB) repair and to compare perinatal outcomes with cases managed using the classic open fetal surgery technique. Methods: In this study, we selected a cohort of consecutive fetuses with isolated open SB referred to our fetal surgery center in Queretaro, Mexico, during a 3.5-year period (2016–2020). SB repair was performed by either classic open surgery (6- to 8-cm hysterotomy with leakage of amniotic fluid, which was replaced before uterine closure) or open microneurosurgery, which is a novel technique characterized by a 15- to 20-mm hysterotomy diameter, reduced fetal manipulation by fixing the fetal back, and maintenance of normal amniotic fluid and uterine volume during the whole surgery. Perinatal outcomes of cases operated with the classic open fetal surgery technique and open microneurosurgery were compared. Results: Intrauterine SB repair with a complete 3-layer correction was successfully performed in 60 cases either by classic open fetal surgery (n = 13) or open microneurosurgery (n = 47). No significant differences were observed in gestational age (GA) at fetal intervention (25.4 vs. 25.1 weeks, p = 0.38) or surgical times (107 vs. 120 min, p = 0.15) between both groups. The group with open microneurosurgery showed a significantly lower rate of oligohydramnios (0 vs. 15.4%, p = 0.01), preterm rupture of the membranes (19.0 vs. 53.8%, p = 0.01), higher GA at birth (35.1 vs. 32.7 weeks, p = 0.03), lower rate of preterm delivery <34 weeks (21.4 vs. 61.5%, p = 0.01), and lower rate of perinatal death (4.8 vs. 23.1%, p = 0.04) than the group with classic open surgery. During infant follow-up, the rate of hydrocephalus requiring ventriculoperitoneal shunting was similar between both groups (7.5 vs. 20%, p = 0.24). All patients showed an intact hysterotomy site at delivery. Conclusion: Intrauterine spina repair by open fetal microneurosurgery is feasible and was associated with better perinatal outcomes than classic open fetal surgery.