OBJECTIVE: To evaluate the effectiveness of intracytoplasmic sperm injection (ICSI) in improving fertilization rates compared to conventional in vitro fertilization rates (IVF) among women aged ≥38 years with a non-male factor diagnosis. DESIGN: Systematic review and meta-analysis. SETTING: Not applicable. PATIENT(S): Women aged ≥38 years with a non-male factor diagnosis receiving IVF or ICSI. INTERVENTION(S): A systematic review of databases including PubMed and Embase was performed. Study protocol was registered at the International Prospective Register of Systematic Reviews. Studies were selected if they compared fertilization rates from ICSI with those from conventional IVF among women aged ≥38 years with a non-male factor infertility diagnosis. A random effects model was used. Meta-analysis of Observational Studies in Epidemiology guidelines were applied. MAIN OUTCOME MEASURE(S): Fertilization rate. RESULTS: Seven studies including 8796 retrieved oocytes (ICSI: 4,369; IVF: 4,427) with mean female age ≥38 years met the inclusion criteria. There was no significant difference in fertilization rates between ICSI and conventional IVF (relative risk [RR] 0.99, 95% confidence interval [CI] 0.93-1.06; P = .8). Heterogeneity was observed between studies (I = 58.2; P < .05). Heterogeneity was significant (I = 57.1; P < .05) when cycles with prior fertilization failure were excluded; however, when analysis was restricted to poor responders (RR 1.01, 95% CI 0.97-1.05; P = .6), heterogeneity was no longer significant (I = 0.0; P = .5). CONCLUSIONS: No difference was found in fertilization rates between conventional IVF and ICSI. Further studies are needed to assess the impact of ICSI in this population, controlling for other indications such as preimplantation genetic testing.