Background: Despite the increased access to effective combination ART, there is still significant mortality associated with malignancies in HIV-positive patients. Because majority of patients present late especially with advanced disease, some of whom may not be able to tolerate standard dose chemotherapy, the Uganda Cancer Institute utilizes both standard dose and dose-modified CHOP chemotherapy for HIV-related NHL. We evaluated HIV patients with NHL treated with standard dose or dose-modified CHOP with the aim of accessing treatment outcomes. Methods: A retrospective cohort study was conducted among patients who received chemotherapy at the UCI between January 2004 to December 2014. 410 eligible patients were reviewed and information on clinical characteristics, chemotherapy regimens, treatment outcomes and vital status at 6-months after completion of chemotherapy. Results: Overall 450 patients were available for screening, 12 did not receive chemotherapy and 37 received other chemotherapy regimens. 410 patients with HIV-related NHL were analyzed with 291 receiving standard dose and 119 patients received dose-modified CHOP chemotherapy. Most patients were male 59.8% and 50.4% in standard dose and dose-modified group respectively. 83.2% in the standard dose and 79.8% in the dose-modified group had advanced disease. A complete response was achieved in 67 of the 291 (23%) patients who received 6 standard dose chemotherapy cycles and 32 of the 119 (27%) patients who received 6 cycles dose-modified chemotherapy. The overall mortality was (18/202) 8.9%; 13/143 (9.1%) in the standard dose group and 5/59 (8.5%) in the dose-modified group. On multivariate analysis, female gender (OR 1.71, 95% CI 1.02-2.85, at least 6 cycles of chemotherapy (OR 0.31, 95% CI 0.11-0.87), chemotherapy received on schedule (OR 0.52, 95% CI 0.30-0.90) and disease progression (OR 3.58, 95% CI 1.01-12.63) were significantly associated with mortality. Conclusions: The complete response rates and mortality were not different; thus, recommendation is to consider dose-modified therapy because of the fewer associated side effects and lesser chemotherapy associated toxicities. Although, this was not statistically significant.