This study included the reveal of the Cytogenetic effects of 6- Thioguanine and methotrexate in lymphocytes obtained from bladder cancer patients, in which we study the effects of those drugs on the blood samples obtained from patients and apparently health individuals, the patients were diagnosed in Al- Yarmouk Hospital. In this study Mitotic index, blastogenic index, chromosomal aberrations, and micronucleus, were employed in the present study as cytogenetic parameters for the mentioned drugs. The most prominent findings of the present work were: 1.The males with bladder cancer showed the highest level of resistant to both drugs. 2.When the patients' cells were treated with 6 - TG, and MTX in - vitro, it reduced MI, but as an over all view, the patients show resistance to 6- TG, and MTX when compared with the control group. 3.When the patients' cells were treated with 6 -TG and MTX in - vitro, it reduced the BI, but as an over all view, the patients show resistance to 6- TG, and MTX when compared with the control group. 4.The chromosomal aberrations frequencies of the patients had increased slightly when treated with the 6- TG. 5. When the patients were treated with MTX, no significant increase in the chromosomal aberrations was observed. 6.The Micronuclei frequency was scored for the patients after treatment with the 6- TG and MTX in - vitro where there was no significant change in its ratio.