Abstract Background Maintaining vascular access for hemodialysis (HD) is a major source of hospitalization, and patient morbidity. In cases of recently thrombosed arteriovenous access (AVA), minimally invasive thrombolysis and adjunctive angioplasty is considered as a reasonable management to restore patency & function of AVA. Objectives The study aims to compare the efficacy and safety of using two different doses (6ml vs 10ml) of recombinant tissue plasminogen activator (rTPA) for pulse-spray thrombolysis of AVA. Methods A Prospective randomized controlled clinical study conducted at Ain -shams university hospitals during the period from July 2022 to December 2022 on 32 patients with recently thrombosed AVAs recruited for ultrasound guided Pulse-Spray Thrombolysis followed by angiography +/- balloon dilatation of the stenosed segments. Patients were included in the study if their AVAs were mature, the duration of AVA thrombosis didn’t exceed two weeks and had no contraindications for rTPA. Patients had been divided randomly into two equal groups by closed envelops method, Group I received 6ml rTPA, Group II received 10ml rTPA, and followed up for six weeks post procedure. Results The immediate post-procedure technical success was 100% in both study groups. Clinical success was 81.25% in group I, and 93.75% in group II (P-value = 0.285), With mean period from thrombolysis till resuming HD 2.769 ± 1.878 days in group I, and 4.00 ± 2.726 days in group II (P-value =0.183). No mortality cases reported, no statistically significant difference between the two groups regarding the procedure- related complications. Conclusions Both doses were effective, we didn’t find statistically significant difference between the two groups as regard clinical and technical success, but using dose of 10ml rTPA yields slightly higher clinical success and longer patency than using 6ml with no statistically significant increase in the rate of adverse effects.