OBJECTIVES: The purpose of the current meta-analysis was to compare the efficacy of lipegfilgrastim (LIP) to pegfilgrastim (PEG) and filgrastim (FIL).  METHODS: EMBASE was searched for head-to-head trials examining the efficacy of LIP, PEG, or FIL. Outcomes included incidence of febrile neutropenia (FN), incidence of severe neutropenia (SN), duration of SN (DSN), and time to recovery of absolute neutrophil count (ANC). Direct comparisons of SN/FN between LIP and PEG were made using random-effects models estimating relative risk (RR). No trials directly compared LIP and FIL; indirect comparisons were made with PEG or placebo/no treatment (PLA) as the common comparator. For DSN/ANC recovery, generic inverse variance methods were employed. RESULTS: Sixty-five studies were identified and 24 were included after full-text review and quality assessment via PRISMA criteria. Over all treatment cycles, LIP was non-inferior to PEG for risk of FN (RR 0.34, 95% CI: 0.05, 2.14). The indirect estimate of FN for LIP versus FIL was also non-significant (RR 0.22, 95% CI: 0.03, 1.51). For SN during cycle 1, LIP had a RR of 0.80 (95% CI: 0.63, 1.03) versus PEG and 0.79 (95% CI: 0.61, 1.03) versus FIL. For subsequent cycles, the RR was 0.53 (95% CI: 0.35, 0.79) LIP versus PEG and 0.45 (95% CI: 0.27, 0.75) versus FIL. Time to ANC recovery was significant: -1.75 days (95% CI: -2.61, -0.90) for LIP versus PEG and ‑1.88 days (95% CI: -2.82, ‑0.95) for LIP versus FIL. No comparions were significant for DSN.  CONCLUSIONS: LIP showed non-inferiority to PEG for risk of at least one FN episode and SN in cycle 1. LIP was more effective than both PEG and FIL for prevention of SN in cycles 2-4 and reduced ANC recovery time. However for DSN differences were not significant. These results suggest that LIP is a possibly more effective treatment.