WHAT THIS PAPER ADDS Current thrombolysis protocols for peripheral arterial occlusions are based on evidence from randomised controlled trials performed >20 years ago. To this day, there is no consensus on the optimum fibrinolytic agent or dose regimens to use. Numerous devices and techniques, such as mechanical thrombectomy and ultrasound assisted thrombolysis, have been proposed and investigated to improve the results of thrombolysis. Major bleeding complications remain a substantial clinical problem of thrombolytic therapy. The present systematic review of the literature provides an update of all reported patient cohorts with peripheral arterial occlusions treated by catheter directed thrombolysis. Objective: Catheter directed thrombolysis (CDT) for peripheral arterial occlusions is a well established alternative to thrombo-embolectomy in patients with (sub)acute limb ischaemia. However, protocols are heterogeneous and need optimisation to improve results and lower bleeding risks. The objective was to review the results and outcomes of different CDT protocols for patients with peripheral arterial occlusions. Data sources: Electronic information sources (MEDLINE, Embase, Cochrane) and reference lists were searched to identify studies reporting results of CDT of peripheral arterial occlusions. Methods: Two independent observers performed study selection, quality assessment and data extraction. Primary outcomes were treatment duration, success rates, and bleeding complications. Secondary outcomes were mortality and amputation rates. Results: One hundred and six studies were included: 19 randomised controlled trials (RCTs), 38 prospective studies, 48 retrospective studies, and one mixed cohort study. The studies comprised a total number of 10,643 cases of which 9877 received CDT for lower extremity arterial occlusion, with a mean treatment duration of 21.4 h (95% confidence interval [CI] 21.0e21.8), an angiographic patency of 75% (95% CI 74.6e 75.1), and freedom from amputation rate of 91% (95% CI 90.3e90.7). Pooled results showed a thrombolysis duration with high dose protocols of 21.9 h (95% CI 21.4e22.5) and 32.7 h with low dose protocols, with bleeding rates of 16.7% (95% CI 16.3e17.1) and 13.4% (95% CI 12.8e14.0), respectively. Weighted mean results for all RCTs and prospective cohorts of >100 cases analysed separately, showed comparable results to all observational cohorts pooled. Bleeding complications occurred in 18% (95% CI 17.8e18.3) of patients and remain an important risk of CDT. Conclusion: CDT is an effective treatment for peripheral arterial occlusions, the main concern is bleeding complications. Although no formal meta-analysis could be performed, the pooled results suggest that lower doses of fibrinolytics lead to similar success rates at a cost of longer treatment duration but with less bleeding. There is large variation in treatment protocols and the available literature suffers from absence of reporting standards and high heterogeneity.