Nonmyeloablative conditioning is less toxic and results in initial establishment of mixed hematopoietic T cell chimerism for up to half a year with prolonged presence of host T cell immunity. In this study, we examined whether this translates into differences in the risks and/or severity of cytomegalovirus (CMV) infection and disease. We analyzed data from 537 nonmyeloablative (NM-HCT) and contemporaneous 2489 myeloablative hematopoietic cell transplant (M-HCT) recipients. In CMV seropositive recipients, no difference in the overall hazards of CMV infection at any level (adjusted hazard ratio [adj. HR] 0.9, 95% confidence interval [95% CI]: 0.7-1.0, P = .14) was noted; however, NM-HCT was associated with a lower risk of high-grade CMV infection (adj. HR 0.7, 95% CI: 0.5-0.9, P = .02). CMV disease rates were similar between the groups during the first 100 days after HCT, but NM-HCT recipients had an increased risk of late CMV disease (adj. HR 2.0, 95% CI 1.2-3.4). The increased risk of late CMV disease after NM-HCT was pronounced during the earlier years of the study period, but not detectable in more recent years. Contrary to earlier reports, survival following CMV disease was not reduced after NM-HCT when compared to M-HCT recipients. These results suggest that residual host cells after NM-HCT reduce progression to higher CMV viral load in NM-HCT recipients; however, this effect does not appear to protect against serious complications of CMV. Therefore, CMV prevention strategies in NM-HCT recipients should be similar to those used in M-HCT recipients.