*Purpose: Incompatible living donor kidney transplantation (ILDKT) recipients require increased immunosuppression compared to their compatible living donor kidney transplant (CLDKT) counterparts. This continued exposure to higher levels of immunosuppression may increase risk of post-transplant cancer.

*Methods: Using USRDS data of Medicare beneficiaries linked to a multicenter cohort study, we compared 471 ILDKT to 4020 CLDKT recipients from 25 US transplant centers from 1999 through 2013. Recipients were determined to have developed post-transplant cancer if they had 1 inpatient (Part A) or ≥2 outpatient claims (Part B) for one of 33 different cancers. We estimated the cumulative incidence of a post-transplant cancer using the Kaplan-Meier method and used stabilized weighted Cox regression to determine the risk of developing cancer in ILDKT vs. CLDKT recipients, adjusting for recipient and transplant-related factors.

*Results: The 5- and 10-year cumulative incidences of post-transplant cancer were 6.1% and 19.7% for ILDKT and 5.7% and 20.8% for CLDKT recipients (Figure 1). After adjustment, ILDKT recipients were 60% less likely to receive a cancer diagnosis compared to CLDKT recipients (stabilized weighted Hazard Ratio [swHR]: _0.18 0.40 _0.90 , p=0.027). However, there were no cancer-specific differences in risk for ILDKT compared to CLDKT recipients after adjustment for multiple comparisons.

*Conclusions: Despite exposure to higher levels of immunosuppression, ILDKT recipients were at decreased risk of developing a post-transplant cancer. While careful monitoring is warranted, this supports the use of ILDKT for recipients when compatible living donors are not available.

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