There is limited evidence on the efficacy of hemostatic powders in the management of upper gastrointestinal bleeding. Provide a pooled estimate of the efficacy and safety profile of hemostatic powders in digestive endoscopy. A computerized bibliographic search on the main databases was performed through December 2018. Pooled effects were calculated using a random-effects model. The primary outcome was immediate hemostasis rate. Secondary outcomes were rebleeding rate (either at 7 and 30 days), bleeding-related mortality, and all-cause mortality rate. A total of 24 studies, of which three were randomized-controlled trials, with 1063 patients were included in the meta-analysis. Immediate hemostasis was achieved in 95.3% (93.3%–97.3%) of patients, with no difference based on treatment strategy, hemostatic agent used, bleeding etiology. Success rate was slightly lower in spurting bleeding (91.9%). Hemostatic powders showed similar efficacy as compared to conventional endoscopic therapy (odds ratio: 0.84, 0.06–11.47; p = 0.9). Thirty-day rebleeding rate was 16.9% (9.8%–24%) with no difference in comparison to other endoscopic treatments (odds ratio 1.59, 0.35–7.21; p = 0.55). All-cause and bleeding-related mortality rates were 7.6% (4%–10.8%) and 1.4% (0.5%–2.4%), respectively. Novel hemostatic powders represent a user-friendly and effective tool in the management of upper gastrointestinal bleeding.