Total marrow and lymphoid irradiation (TMLI) delivers radiation dose to the bone marrow and lymph nodal region while reducing the dose to non-target organs. We conducted a dose-escalation study of TMLI to improve treatment outcomes while reducing OAR doses using intensity-modulated radiation therapy. However, this dose escalation strategy may cause increasing risk of recurrence and adverse events because of dose uniformity compromises of the target. We hypothesized that the homogeneity index (HI) could become worse with increased target's dose while maintaining reduced OAR doses for the nine patients enrolled in the TMLI phase Ⅰ clinical trial. Nine patients treated with TMLI using a treatment delivery system from September 2019 to August 2021 were included. The prescribed doses were 14 Gy/6 fr, 16 Gy/6 fr, and 18 Gy/6 fr twice daily for 3 days, with three patients allocated each prescription. Bone marrow, lymph nodal region, spleen, testis, brain, and liver were designated as targets. The bone marrow was divided into eight parts (see Table); an individual PTV margin was added to each structure. We intended to deliver the D80% prescription dose for PTV. For the brain and liver, the prescribed dose was 12 Gy in consideration of function preservation. Lenses, oral cavity, parotid glands, lungs, heart, esophagus, stomach, kidneys, intestines, and breasts were defined as OAR. Targets were evaluated with HI that was calculated using the formula HI = (D2%-D98%)/D50%, based on ICRU report 83. For OARs, Dmax, D2%, D10%, and mean dose constraint were evaluated. The table lists HI for the PTV_ALL and each target. The HI of PTV_ALL rose with increasing prescription dose and was highest at 18 Gy. The highest HI was 0.632 for PTV_Rib at 18 Gy, and the lowest HI was 0.045 for PTV_testis at 14 Gy. OAR Dose constraints were achieved in all patients. The average OAR doses in all cases for lenses, oral cavity, parotid glands, lungs, heart, esophagus, intestines, kidneys, and breast were 4.7±0.80, 4.4±0.51, 6.7±0.48, 7.6±0.22, 7.8±0.19, 6.7±0.18, 7.4±1.12, 6.9±0.96, and 14.7 Gy, respectively. The Dmax of the lenes, D2% of the esophagus, and D10% of the stomach were 7.2 ± 1.09, 11.5 ± 0.47, and 10.9 ± 0.98 Gy, respectively. In the TMLI phase I clinical trial, we evaluated the dose uniformity to the targets and the OAR dose constraints. Although the HI for PTV_ALL worsened with increasing prescription dose, compliance with OAR dose constraints was achieved in all patients.