Blood transfusion is life-saving but sometimes also associated with morbidity and mortality. There is limited data on mortality in patients transfused with whole blood in sub-Saharan Africa. We described the 30-day all-cause mortality and its associated factors in patients transfused with whole blood to inform appropriate clinical intervention and research priorities to mitigate potential risks. A retrospective study was performed on purposively sampled patients transfused with whole blood at the Uganda Cancer Institute (UCI) and Mulago hospital in the year 2018. Two thousand twelve patients with a median (IQR) age of 39 (28–54) years were enrolled over a four month period. There were 1,107 (55%) females. Isolated HIV related anaemia (228, 11.3%), gynaecological cancers (208, 10.3%), unexplained anaemia (186, 9.2%), gastrointestinal cancers (148, 7.4%), and kidney disease (141, 7.0%) were the commonest diagnoses. Most patients were transfused with only one unit of blood (n = 1232, 61.2%). The 30 day all-cause mortality rate was 25.2%. Factors associated with mortality were isolated HIV related anaemia (HR 3.2, 95% CI, 2.3–4.4), liver disease (HR 3.0, 95% CI, 2.0–4.5), kidney disease (HR 2.2, 95% CI, 1.5–3.3; p<0.01), cardiovascular disease (HR 2.9, 95% CI, 1.6–5.4; p<0.01), respiratory disease (HR 3.0, 95% CI 1.8–4.9; p<0.01), diabetes mellitus (HR 4.1, 95% CI, 2.3–7.4; p<0.01) and sepsis (HR 6.2, 95% CI 3.7–10.4; p<0.01). Transfusion with additional blood was associated with survival (HR 0.8, 95% CI 0.7–0.9, p<0.01). In conclusion, the 30-day all-cause mortality was higher than in the general inpatients. Factors associated with mortality were isolated HIV related anaemia, kidney disease, liver disease, respiratory disease, cardiovascular disease, diabetes mellitus and sepsis. Transfusion with additional blood was associated with survival. These findings require further prospective evaluation.