Epinephrine local injection is a hemostatic procedure used in active diverticular bleeding that elicits vasoconstriction and tamponade effects. We compared the additional benefit of combination therapy with HSE-C (hypertonic saline epinephrine injection with clipping) to clipping monotherapy. Retrospective data on diverticular bleeding between 2011 and 2016 was reviewed. Those with an active bleeding source confirmed by colonoscopy (excluding non-bleeding vessels and adherent clots) who received either HSE-C or clipping were evaluated. Endpoints were rates of successful primary hemostasis, recurrent bleeding, and surgical intervention during hospitalization. A total of 320 patients with diverticular bleeding were evaluated, on which either HSE-C (n = 35) or clipping monotherapy (n = 18) was performed. Rates of successful primary hemostasis (91.4% vs. 66.7%, p = 0.048) and direct placement of endoclips (60.0% vs. 16.7%, p = 0.004) were significantly higher in the HSE-C group. Although not statistically significant, the HSE-C group had a higher rate of early rebleeding (18.8% vs. 8.3%, p = 0.653), while no difference was seen in the number of patients requiring surgery (11.4% vs. 5.5%, p = 0.651). HSE-C is associated with a higher rate of successful primary hemostasis for severe active diverticular bleeding but has no significant difference in reducing early recurrent bleeding or the number of patients requiring surgery, suggesting that hemostatic effects may be temporary.