Background: Patients with arrhythmias, particularly paroxysmal supraventricular tachycardia (PSVT), face an increased risk of cardiac complications. Currently, non-parenteral medications for rapid PSVT cessation are lacking. Etripamil, a novel intranasal, short-acting calcium channel blocker, offers a rapid onset and the potential for unsupervised PSVT management. However, data on its use in arrhythmia management remain limited. Aims: We aimed to assess the efficacy and safety of 70 mg of etripamil compared with placebo in the treatment of PSVT. Methods: We systematically searched PubMed, Embase, Web of Science, Scopus, and the Cochrane Library for randomized controlled trials (RCTs) from inception to April 2025. We calculated pooled risk ratios (RRs) with 95% confidence intervals (CIs) using random or common effects models, depending on the heterogeneity. Results: Four RCTs including 540 patients were analyzed. Etripamil demonstrated higher conversion rates to the sinus rhythm at 15 min (RR 1.84 [95% CI: 1.32–2.48]), 30 min (RR 1.80 [95% CI: 1.38–2.35]), and 60 min (RR 1.24 [95% CI: 1.04–1.48]). PSVT recurrence rates were similar between groups (RR 0.52 [95% CI: 0.20–1.34]). Adverse events (AEs) and severe AEs were comparable between etripamil and the placebo. Etripamil was associated with higher rates of nasal discomfort, nasal congestion, rhinorrhea, and epistaxis but not with increased bradyarrhythmia, atrial fibrillation, or non-sustained ventricular tachycardia. Conclusions: Etripamil appears to be a promising treatment for cardiac arrhythmias. Larger long-term RCTs are needed to confirm its safety and efficacy in clinical practice.