Background: Granulocyte colony-stimulating factors (G-CSFs) include long-acting ones and short-acting ones. They have been mainly applied in Chinese clinical practice for years to prevent neutropenia. However, which type of G-CSF is more superior has not been conclusively determined. Methods: A systematic literature search was conducted using the PubMed, Embase, Cochrane Library, clinical trials.gov, China National Knowledge Infrastructure, and WAN FANG databases for related studies published till August 2021. Revman 5.3 software was used to assess the effectiveness and safety of these 2 types of G-CSFs in patients undergoing chemotherapy. Results: Ten studies involving 1916 patients were included in our meta-analysis to compare the effectiveness and safety of long-acting G-CSFs and short-acting G-CSFs. We found that the incidence of febrile neutropenia (relative risk [RR] 0.82; 95% confidence interval [CI] 0.57–1.17), the recovery time of the absolute neutrophil count (mean difference –0.23; 95% CI –0.49 to 0.03), and the fatigue rate (RR 0.82; 95% CI 0.62–1.07) were similar between the long- and the short-acting G-CSFs. However, the long-acting G-CSFs significantly decreased the incidence (RR 0.86; 95% CI 0.76–0.96) and shortened the duration (mean difference –0.19; 95% CI –0.38 to 0.00) of severe (grade ≥3) neutropenia, and decreased the rate of bone and/or muscle pain (RR 0.75; 95% CI 0.58–0.98). Conclusion: Primary prophylaxis with long-acting G-CSFs was more effective and safer than primary prophylaxis with short-acting G-CSFs in Chinese adults undergoing chemotherapy.