Background: There is evidence that NK cells with low cytotoxicity but strong immunoregulatory characteristics contribute to good graft outcome. We attempted to investigate which NK cell subsets increase post-transplant and might affect graft function. Method: Lymphocyte and NK cell subsets were determined in whole blood using eight-colour-fluorescence flow cytometry in patients pre-transplant and post-transplant. In total, 31 transplant recipients were studied. Results: When cell numbers were compared in 9 patients pre- and 6 months post-transplant, post-transplant CD56dimCD16+ (p = 0.011) NK cells with the phenotype CD158a + (p = 0.008), CD158e+ (p = 0.038), NKG2A+ (p = 0.008), NKG2D + (p = 0.011), IFNyR+ (p = 0.008), perforin + (p = 0.008), granzymeB + (p = 0.008), perforin + granzymeB + (p = 0.008) and perforin-granzymeB- (p = 0.021) were lower than those pre-transplant, indicating a post-transplant reduction of cytotoxic NK cells. In 28 patients NK cell subsets were analyzed with respect to time post-transplant (median 888 days post-transplant). CD56dimCD16+ NK cells co-expressing CD158a (p = 0.014), NKG2D (p = 0.047), IL4R (p = 0.038), IL10R (p = 0.008) and IFNy (p = 0.036) as well as CD56bright NK cells with the phenotype TUF beta+ (p = 0.017), TGFR + (p = 0.035), CD158a + (p = 0.042) and perforin-granzymeB- (p = 0.048) increased with time post-transplant. Conclusion: Post-transplant, cytotoxic NK cells were lower than pre-transplant and remained low, whereas NK cell subsets with potentially immunoregulatory properties increased.