OBJECTIVE. This study tested the hypothesis that underutilization of poison control centers is associated with increased rates of hospitalizations attributable to poisonings in rural areas. METHODS. To measure the potential impact of poison control centers on hospitalization rates in rural areas among people who visit emergency departments because of poisoning, we estimated the reduction in hospitalization rates associated with increased rates of calls to centers. We used the 2003 State Inpatient Database and State Emergency Department Database from the Healthcare Cost and Utilization Project to calculate the numbers of emergency department visits and hospitalizations for each county in the 12 states analyzed. We used Toxic Exposure Surveillance System data from the American Association of Poison Control Centers to calculate the number of human exposure calls per capita according to county. RESULTS. In rural counties, a 1% higher poison control center human poison exposure call rate was associated with a 0.19% lower hospitalization rate among people who visited emergency departments because of poisoning. If the observed association is causative, then 43.3 calls would prevent 1 hospital admission, yielding $7321 in net cost savings and a return on investment of 5.9:1 (from the health care system perspective). CONCLUSIONS. Our results establish the existence of the hypothesized association between rural poison control center utilization rates and hospitalization rates among emergency department-treated poisoning patients.