Deployment of genetically resistant Eastern white pine (Pinus strobus L.) planting stock could reduce economic losses to root rot caused by Phytophthora cinnamomi Rands in Christmas tree and forest plantations. This study aimed to determine the degree of genetic control of resistance to P. cinnamomi in Eastern white pine and secondarily, to compare the aggressiveness of two P. cinnamomi isolates derived from different host species. Phytophthora isolates from Fraser fir (Abies fraseri (Pursh) Poir.) and Eastern white pine were used in a main and supplemental study, respectively, including 83 and 20 open-pollinated families. In each study, two-year-old seedlings were inoculated twice each of two consecutive years and mortality was assessed biweekly for 16 weeks each year. During the first year, mortality increased over time to 18.6% and 40.4% while family variation in mortality ranged from 1.3% to 60.0% and 12.5% to 73.0% in the main and supplemental studies, respectively. At the end of the first year, individual-tree and family-mean heritability estimates were, respectively, 0.44 ± 0.0935 and 0.85 ± 0.180 for the main study, and 0.57 ± 0.216 and 0.90 ± 0.343 for the supplemental study. The P. cinnamomi isolate from Eastern white pine was more aggressive and there was a large interaction between isolates and pine families. Deploying resistant families will be complicated by this interaction but should, nevertheless, reduce economic losses.