Introduction: A network meta-analysis (NMA) was performed to assess the efficacy and safety of avatrombopag, relative to eltrombopag, romiplostim, and fostamatinib, for patients with chronic immune thrombocytopenia (ITP) not responding adequately to corticosteroids. Methods: A systematic search of publication and clinical trial databases was conducted to identify relevant randomized controlled trials (RCTs) and observational studies. Data from eligible studies were extracted and analyzed in a Bayesian framework using relative effect sizes vs placebo. Outcomes included durable platelet response; need for rescue therapy; reduction in use of concomitant ITP medication; incidence of any or World Health Organization (WHO) grade 2–4 bleeding events, and any adverse events. Results were reported as odds ratios or incidence rate ratios (IRR) with 95% credible intervals (CrIs). Results: The NMA included seven phase 3 RCTs. Compared with placebo, avatrombopag was associated with statistically significant improvements in durable platelet response, reduction in use of concomitant ITP medication, and incidence of any bleeding events. Statistically significant differences vs placebo were also observed for durable platelet response and need for rescue therapy (eltrombopag, romiplostim, and fostamatinib); reduction in use of concomitant ITP medication (eltrombopag and romiplostim); incidence of any bleeding events (fostamatinib); and incidence of WHO grade 2–4 bleeding events (romiplostim and fostamatinib). No statistically significant differences were observed for any adverse events. Avatrombopag was associated with a statistically significant lower incidence of any bleeding events vs eltrombopag (IRR 0.38 [95% CrI 0.19, 0.75]) and romiplostim (IRR 0.38 [95% Crl 0.17, 0.86]); no other between-treatment differences were observed. Conclusion In this NMA, avatrombopag significantly increased the chance of achieving durable platelet response and reducing the use of concomitant ITP medication vs placebo, and significantly reduced the incidence of any bleeding events compared with placebo, eltrombopag, and romiplostim. The study aims to help guide clinicians managing patients with chronic ITP and insufficient response to previous treatment.