To investigate the effectiveness and safety of office hysteroscopic metroplasty by diode laser for the treatment of septate uteri. We performed a prospective cohort study including 41 nulliparous women diagnosed with septate uterus and a history of primary infertility or recurrent miscarriage. All patients underwent hysteroscopic metroplasty for the treatment of the uterine septum, which was performed in-office setting using a 4.3 mm continuous-flow hysteroscope and a 15-watt diode laser at 1470 nm. Surgical and reproductive outcomes after 2 years of follow-up are reported. The procedure was well tolerated by 93% of patients. No surgical complications were reported. Thirty women out of 38 (78.9%) became pregnant: 17 (56.7%) pregnancies were spontaneously conceived, and 13 (43.3%) were obtained with assisted reproductive techniques. Twenty-four (80%) of the 30 pregnant women had a live birth, with a cumulative live birth of 63.2% among the 38 women (95% CI: 45.9–78.2%). There were no cases of post-partum hemorrhage or uterine rupture among 14 (58.3%) women who had vaginal deliveries. Office hysteroscopic metroplasty for septate uterus using diode laser appears to be a feasible and safe alternative to other available techniques and has sufficient efficacy in terms of reproductive outcomes to be considered for further investigations.