Background Hematological abnormalities are common in pulmonary tuberculosis (PTB) patients, which is one of the major public health problems worldwide. However, there is paucity of information about the hematological profile of PTB patients with and without HIV in the study area. Therefore, this study aimed to assess hematological abnormalities of pulmonary tuberculosis patients with and without HIV at the University of Gondar Hospital, Northwest Ethiopia. Methods A comparative cross-sectional study was conducted at the University of Gondar Hospital. Sociodemographic data was collected using a pretested, structured questionnaire. Five milliliters of venous blood sample was collected and divided into a 3 ml EDTA tube for complete blood count with the Cell Dyn 1800 hematological analyzer and a 2 ml citrated tube for erythrocyte sedimentation rate determination. Data were entered into Epi Info version 3.5.3 and then transferred to SPSS 20 for analysis. The independent samples t-test was used to compare the mean values of hematological parameters between PTB patients and PTB-HIV coinfected patients. Result A total of 100 study subjects (50 PTB and 50 PTB-HIV coinfected) were included with a mean age of 31.3 ± 10.3 years for PTB patients and 32.1 ± 9.2 years for PTB-HIV coinfected patients. In this study, there were significantly lower mean values of Hgb (P = 0.049), platelet count (P < 0.001), and neutrophils counts (P = 0.007) among PTB-HIV coinfected patients when compared with PTB patients. Of the PTB infected patients 46% were anemic, 6% leukopenic, 22% neutropenic, 8% lymphopenic, and 8% thrombocytopenic. On the other hand, of the PTB-HIV coinfected patients 60% were anemic, 14% leukopenic, 66% neutropenic, 12% lymphopenic, and 20% thrombocytopenic. ESR value was increased in all patients. Conclusion This study demonstrated high prevalence of neutropenia, anemia, and thrombocytopenia among PTB-HIV coinfected patients. HIV coinfection worsens hematological abnormalities of PTB patients. Assessment of hematological parameters can be used as an indicator in the diagnosis and follow-up of PTB patients coinfected with HIV. We recommended assessment of PTB patients with or without HIV for various hematological disorders such as neutropenia, anemia, and thrombocytopenia.