Prior to 2010, the introduced population of American bison (Bison bison) on Santa Catalina Island, California, was managed through the shipment of surplus bison to private ranches, Native American reservations, and livestock auctions on the mainland. In response to escalating costs, transport-induced stress to the animals, and ecologic impacts associated with high bison numbers on-island between shipments, the use of the immunocontraceptive vaccine porcine zona pellucida (PZP) as a fertility control option for managing the population was investigated. Between 2009 and 2012, a total of 64 bison cows (≥1 yr old) received primer inoculations of 100 μg PZP emulsified with 0.5 ml Freund's modified adjuvant (FMA) delivered through a combination of intramuscular injections by hand (50 bison cows) during roundups and via field darting (14 bison cows). Pre-rut booster inoculations of 100 μg PZP emulsified with 0.5 ml Freund's incomplete adjuvant (FIA) were administered exclusively via field darting in 2010, 2011, and 2012 to 45, 48, and 61 bison cows (≥1 yr old), respectively. During the present study, 38 adult cows (marked and unmarked) received one or more PZP inoculations during their first, second, or third trimesters of pregnancy, and of these individuals, 35 successfully produced calves. Low pregnancy values detected in the remaining three cows have been attributed to residual progesterone associated with unsuccessful fertilization. The 2010 pretreatment calving rate (calves born per cow) determined via direct observation was 67.4% (29 calves from 43 cows). Through the use of PZP, the calving rate was reduced to 10.4% by 2011 and to 3.3% by 2012. Considering the annual mortality rate of 2–5% documented during this study, the results demonstrate the potential of PZP use as an effective nonlethal tool for controlling population growth in free-ranging bison.