BackgroundMother-to-Child Transmission of HIV accounts for more than 90% of all pediatric HIV infections. Ethiopia has recently adopted lifelong antiretroviral therapy (ART) for all HIV-positive pregnant and breastfeeding women (Option B+ strategy), regardless of CD4 count or clinical stage. Therefore, the aim of this systematic review and meta-analysis was to estimate the pooled incidence and predictors of loss to follow-up among pregnant and lactating mothers living with HIV and enrolled in HIV care clinics in Ethiopia.MethodThe Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline was followed. All observational published studies were retrieved using relevant search terms in PubMed, Google Scholar, Cochrane Library, Scopus, African Journals Online, CINHAL, and Ethiopian's university research repository online library. STATA 11 software was used to analyze the data. The Cochrane Q and I2 tests were used to assess the heterogeneity of studies. The pooled estimated prevalence and odds ratios with 95% confidence intervals were computed by a random-effects model.Result: The pooled magnitude of loss to follow-up among pregnant and lactating mothers living with HIV and enrolled in HIV care clinics in Ethiopia was 14.28% (95%CI: 10.12-18.44). Poor/fair antiretroviral treatment adherence (Adjusted odds ratio (AOR) = 3.68; 95% CI: 2.89–4.69), who does not know their CD4 level (AOR = 3.68; 95% CI: 2.40–5.63), disclosure of HIV status to partner (AOR = 2.69; 95% CI: 2.08–3.48), experienced drug side effect (AOR =7.91; 95% CI: 2.94–21.33), residing in the rural area (AOR =2.66; 95% CI: 2.34–3.03), and no education (AOR =4.28; 95% CI: 3.62–5.00) were the significant predictors of loss to follow up.ConclusionThe magnitude of loss to follow-up among pregnant and lactating mothers was high in Ethiopia. Thus, counseling, strengthening the linkage and referral system, establishing appropriate tracing mechanisms, and determining CD4 level is crucial to decrease loss to follow-up among pregnant and lactating mothers living with HIV.