Clinical guidelines for acute lower gastrointestinal bleeding (LGIB) recommend non-endoscopic treatment when endoscopic treatment is difficult or the patient is hemodynamically unstable. The aim of this study was to investigate whether angiography should be prioritized as initial treatment for severe LGIB patients over colonoscopy. Methods: We undertook a retrospective cohort study using the Japanese Diagnosis Procedure Combination inpatient database. We compared adult patients who underwent colonoscopy or angiography within 1 day of admission for severe LGIB from 2010 to 2017. The primary outcome was in-hospital mortality. Secondary outcomes included surgery carried out within 1 day after admission and surgery carried out between 2 and 7 days of admission. Propensity score-matched analyses were undertaken to adjust for confounders. Results: We identified 6,546 eligible patients. The patients were divided into the colonoscopy group (n = 5,737) and angiography group (n = 809). After one-to-four propensity score matching, we compared 3,220 and 805 patients who underwent colonoscopy and angiography, respectively. The angiography group was not significantly associated with reduced in-hospital mortality compared with the colonoscopy group. In contrast, the number of patients who underwent surgery within 1 day of admission was significantly lower in the angiography group than in the colonoscopy group. Conclusions: The present study revealed that in-hospital mortality did not significantly differ between colonoscopy and angiography, even in severe LGIB patients. Although this study was unable to identify which subgroups should undergo angiography for primary hemostasis, angiography might be a better option than colonoscopy for initial hemostasis in more severe cases of LGIB.