Mining operations in northern Ontario, Canada, have generated substantial quantities (50–100 million tons by dry weight) of pyrrhotite tailings over recent decades. Untreated tailings containing up to 1 wt% of Ni are considered waste and can cause acid mine drainage (AMD). To mitigate the potential AMD hazards due to atmospheric oxidation, these tailings are stored underwater. Metso’s BIOX® process is well-known for its commercial success in treating gold-bearing sulfide minerals, primarily pyrite, due to its simplicity and robustness. This study aims to test the BIOX® bioleaching process for nickel extraction from pyrrhotite. Semi-batch BIOX® bioleaching experiments were conducted to investigate the efficiency of nickel extraction, the elemental sulfur yield, as well as the optimal combination of pH levels in each stage. Based on experimental data, the process was modeled with the HSC software and compared with a two-step process we have previously studied.