Background Accurately differentiating pneumocystis from cytomegalovirus pneumonia is crucial for correct therapy selection in AIDS patients. Hence, the goal of this study was to compare the CT features of pneumocystis pneumonia and cytomegalovirus pneumonia in AIDS patients and identify clinical hallmarks to accurately distinguish these two pathologies.Methods A total of 112 AIDS patients (78 with pneumocystis pneumonia and 34 were cytomegalovirus pneumonia) were included in this study. Two experienced chest radiologists retrospectively reviewed CT images for 17 features including ground-glass opacity, consolidation, nodules, and halo sign. Significance was calculated by the chi-square (χ2) test.Results The presence of consolidation (61.77% in cytomegalovirus pneumonia, 35.9% in pneumocystis pneumonia, p=0.011), halo signs (32.35% in cytomegalovirus pneumonia, 11.54% in pneumocystis pneumonia, p<0.001), and nodules (47.06% in cytomegalovirus pneumonia, 8.97% in pneumocystis pneumonia, p<0.001), especially small nodules (32.5% in cytomegalovirus pneumonia, 6.41% in pneumocystis pneumonia, p<0.001) without perilymphatic distribution, were significantly more frequent in patients with cytomegalovirus pneumonia than in those with pneumocystis pneumonia. Large nodules were not found in any of patients with cytomegalovirus pneumonia. The presence of ground-glass opacity (100% in pneumocystis pneumonia and cytomegalovirus pneumonia), reticulation (57.69% in pneumocystis pneumonia, 52.94% in cytomegalovirus pneumonia, p=0.782) and bronchial wall thickening (34.62% in pneumocystis pneumonia, 47.06% in cytomegalovirus pneumonia, p=0.213) were common in both groups. Conclusions Analysis of consolidation, nodules, and halo signs may contribute to the differential diagnosis of pneumocystis pneumonia or cytomegalovirus pneumonia. However, some CT features considered typical in one or other diseases appear with similar frequency in both cohorts of AIDS patients.