Background: CMV reactivation after allo-HSCT has been shown to be associated with decreased risk of early relapse. We sought to evaluate the effects of two T cell depletion strategies on the incidence of CMV reactivation, risk of relapse, and survival data between the two cohorts. Methods: We retrospectively evaluated all charts of patients (pts) who underwent allo-HSCT between 2005-2015. Data were collected and the two cohorts divided into alemtuzumab (A) vs. anti-thymocyte globulin (ATG). Results: There were 55 pts in ATG group and 38 in A. Both groups were similar with respect to age, gender, intensity of conditioning regimens, diagnosis, remission status at transplant, aGVHD and HLA mismatch. CMV positivity in donor, recipient or both was present in 81% of cases in ATG group and 62% of cases in A (P = 0.04). There was no difference in ATG and A groups with respect to CMV reactivation (P = 0.86), or relapse at 1 year (yr) (P = 0.34). There was no difference in CMV reactivation between myeloablative (MAC) and reduced intensity conditioning (RIC). There was more CMV reactivation at 100 days in pts with myeloid malignancies (P = 0.036). Of pts without CMV reactivation at 100 days, 36% relapsed at 1 yr vs. 12% with CMV reactivation at 100 days (P = 0.02). Consequently there was an improvement in relapse free survival (RFS) with CMV reactivation (P = 0.02). There was no impact of the T cell depletion strategy, nor the intensity of conditioning regimen on RFS. Overall survival (OS) was better with A than with ATG (P = 0.004) but was not impacted by CMV reactivation or intensity of conditioning regimen. The hazard of CMV reactivation was decreased by 16% in ATG arm but was not statistically significant. Nonrelapse mortality (NRM) was significantly higher in ATG group compared to the A group (P = 0.02), and in the MAC group compared to the RIC group (P = 0.047). Conclusions: CMV reactivation at 100 days significantly decreased the risk of relapse at 1 year thereby improving RFS. However, the use of ATG vs. A did not impact the risk of CMV reactivation or relapse. Interestingly, OS was improved with A and NRM was higher with ATG, warranting further prospective evaluation.