Objective To compare the outcome of monochorionic diamniotic (MCDA) twin pregnancies conceived by in‐vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) with that of spontaneously conceived MCDA twins. Methods This was a retrospective cohort study of MCDA twin pregnancies conceived after IVF/ICSI or spontaneously, followed from the first trimester onwards at a single center between January 2002 and September 2018. The primary outcome was survival per fetus from the first trimester until 28 days after birth. Secondary outcome measures were number of survivors, miscarriage, termination of pregnancy, intrauterine and neonatal death, major congenital anomalies, twin–twin transfusion syndrome, selective fetal growth restriction, gestational age at birth, delivery before 32 weeks' gestation, mode of delivery, admission to the neonatal intensive care unit, birth weight and birth‐weight discordance. Results Of the 654 MCDA pregnancies included in the analysis, 80 were conceived by IVF/ICSI and 574 spontaneously. Overall fetal and neonatal survival was significantly lower in the IVF/ICSI group than in the spontaneous‐conception group (79% vs 90%; P = 0.001). In the IVF/ICSI group, compared with the spontaneous‐conception group, loss of one or both twins occurred twice as often (29% vs 14%; P = 0.001) and there was a higher risk of second‐trimester miscarriage (8% vs 1%; P = 0.002). Conclusions MCDA twins conceived after IVF/ICSI have lower overall survival rates and higher rates of second‐trimester miscarriage than do spontaneously conceived MCDA twins. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.