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Background Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition caused by persistent obstruction of the pulmonary arteries. While pulmonary endarterectomy is curative in eligible patients, many are inoperable due to distal thrombi or comorbidities. Balloon pulmonary angioplasty (BPA) and riociguat, a soluble guanylate cyclase stimulator, are treatment options in this group, yet comparative efficacy remains uncertain. We aimed to systematically review and meta-analyse randomised controlled trials (RCTs) comparing BPA and riociguat in inoperable CTEPH.Methods A comprehensive literature search was conducted across PubMed, Embase, Cochrane CENTRAL, and ClinicalTrials.gov from January 2018 to April 2025, following PRISMA guidelines. Eligible studies were RCTs comparing BPA and riociguat in adult patients with confirmed inoperable CTEPH. Outcomes included mean pulmonary arterial pressure (mPAP), cardiac output (CO), pulmonary vascular resistance (PVR), mean right atrial pressure (mRAP), and NT-proBNP levels. Data extraction and quality assessment were conducted independently by two reviewers. A random-effects model was used for pooled estimates, with heterogeneity assessed by I 2 statistics and sensitivity analyses.Results Three RCTs involving 262 patients (134 BPA, 128 riociguat) were analysed. BPA led to a significantly greater reduction in mPAP (MD: 12.23 mmHg; 95% CI: 9.15–15.32; p < 0.00001) and pulmonary vascular resistance (MD: 208.58 dyn·s/cm 5; 95% CI: 117.32–299.85; p < 0.00001), with both outcomes showing initial heterogeneity that resolved upon sensitivity analysis. BPA also reduced mRAP more than riociguat (MD: 2.18 mmHg; 95% CI: 1.23–3.13; p < 0.00001). NT-proBNP levels, a biomarker of cardiac stress, decreased more substantially with BPA (MD: 989.61 pg/mL; 95% CI: 522.55–1456.66; p < 0.0001). In contrast, riociguat was superior in improving CO (MD: 0.47 L/min; 95% CI: 0.37–0.58; p < 0.00001), suggesting a distinct mechanism of benefit. All outcomes showed consistency across studies except for one trial identified as a source of heterogeneity that resolved upon sensitivity analysis. No significant difference was found in overall adverse event rates, though BPA carried procedural risks including pulmonary injury.Conclusion BPA offers superior hemodynamic and biomarker improvements over riociguat in inoperable CTEPH, whereas riociguat enhances cardiac output. A patient-specific approach considering feasibility and treatment goals may optimise outcomes.