The use of mammalian oocytes to assess human sperm functionality could be a helpful tool with potential applications in clinical and research programs. In an attempt to develop the pig model, the aim of the present work was to study the interaction between human spermatozoa and pig oocytes at the zona pellucida (ZP), the oolemma, and the ooplasm levels. In vitro matured pig oocytes and human spermatozoa from fertile and low-fertility donors were employed. The induction of the acrosome reaction by the ZP, the ability of the sperm to penetrate the oocyte after coincubation, and the male pronuclear formation after ICSI were evaluated. Human spermatozoa can bind to pig ZP and undergo the acrosome reaction (15% to 58%, depending on the individual); they are not able to fuse with the oolemma but they can decondense and form a male pronucleus (40%-100%) when injected into pig oocytes. In conclusion, this study shows that pig oocytes can be a useful model to assess human sperm functionality.