Rituximab (RIT) induction therapy is widely used for desensitization against ABO-incompatible living-donor kidney transplants (KT). However, the efficacy of valganciclovir (VGCV) prophylaxis against cytomegalovirus (CMV) disease and infection in KT recipients (KTRs) following RIT induction remains unclear. The current multicenter retrospective study included 213 KTRs who received low-dose RIT induction between 1998 and 2021, across 6 facilities included in the Michinoku Renal Transplant Network (MRTN). VGCV dosage varied from 450mg/day (twice weekly) to 900mg/day (daily), with treatment durations of 3-12months. The primary and secondary endpoints were the incidence of CMV disease and infection, respectively. The incidence of CMV disease was significantly higher in the VGCV group (23.5%; 16 patients) than in the non-VGCV group (5.5%; 8 patients) (p < 0.01). The incidence of CMV infection was 54.5% (79 patients) in the non-VGCV group and 48.5% (33 patients) in the VGCV group, with no significant difference (p = 0.42). In the subgroup of CMV-seronegative KTRs receiving allografts from CMV-seropositive donors (CMV IgG (D + /R-)), 18 out of 24 KTRs received VGCV prophylaxis, of whom 10 (55.6%) developed CMV disease. Within this subgroup, only 4 KTRs received VGCV with the standard protocol (900mg daily for 6months), and none developed CMV disease. Insufficient VGCV prophylaxis does not reduce the incidence of CMV disease in KTRs following low-dose RIT induction. Despite concerns about leukopenia due to RIT and VGCV, in KTRs with CMV IgG (D + /R-) serostatus, VGCV prophylaxis with a standard protocol may be advisable.