To assess the effectiveness of intracytoplasmic sperm injection (ICSI) combined with piezoelectric stimulation in infertile couples with a history of total fertilization failure (TFF).Prospective controlled trial.Clinical IVF laboratory.Seventy-one couples undergoing ICSI on sibling oocytes having at least one previous ICSI attempt with TFF.ICSI or ICSI with piezoelectric activation.Fertilization rate.The patients were allocated to two groups: group I included 21 patients with only one previous TFF and group II included 50 patients with more than one previous TFF. Collectively, a total of 823 metaphase II (MII) oocytes were retrieved in 78 oocyte retrievals. In Group I, combined ICSI with piezoelectric stimulation was applied to 123/211 (58.2%) of MII oocytes (group IA), whereas standard ICSI procedure was applied to 88/211 (41.8%) of MII oocytes (group IB). The fertilization rate was 62% and 12% in group IA and group IB respectively. In group II, piezoelectric activation was applied in all 612 MII oocytes, of which 296 (48.3%) were fertilized. The rates for implantation and pregnancy/embryo transfer were obtained as 30.6% and 44.1%, respectively.Piezoelectric activation seems to improve IVF outcome in patients with previous TFF history.