Abstract Funding Acknowledgements Type of funding sources: None. Introduction While considered the gold standard for cardiac perfusion imaging and myocardial blood flow quantitation, the use of 15O-water has been largely restricted to research purposes. The practical hurdles associated with the ultra-short half-life of the tracer and the lack of dedicated software have hampered the routine clinical use of 15O-water and novel solutions have been sought to obviate the issues limiting its use. An innovative bedside 15O-water generator designed for simple push button operation and high patient through-put has been developed and recently installed at our institution and utilized clinically under a magistral exception. The system also includes an infusion device and a dedicated display and analysis software. We report the initial experience utilizing such solution for routine clinical use of 15O-water. Methods The first routine human myocardial perfusion imaging tests with PET 15O-water were conducted at our institution in December 2020. The 15O-water was produced and infused using the bed-side water generator. The activity per scan was 400 MBq in 20-35 mL of saline infused at a speed of 1-2 mL/s. Each exam consisted of a low-dose CT followed by a 4 min rest dynamic PET scan and, finally, a 4 min stress dynamic PET scan. Pharmacological stress was induced using a 6 min infusion of adenosine (0.14 mg/kg/min) starting 2 min prior to the stress PET scan. The exam time (time from initiation of the low dose CT to the end of the stress PET scan) was monitored. Images were analyzed using the dedicated software. Results Since its implementation on December 7, 2020 and as of February 23, 2021, all patients referred to the hospital for cardiac perfusion imaging have been studied with this approach. Over this period of time, a total of 295 patients have been imaged with an average of 6 patients per day (a total of 50 scan days, 3-8 patients per day). The median total exam time was 22 min (85% of the exams were within 25 min and 95% below 30 min). Conclusion Routine clinical use of 15O-water PET has been practically implemented utilizing a novel bedside generator and infusion solution. The system has proven to be reliable and efficient. This initial experience suggests that a very high patient throughput is achievable with improved resource utilization. The expected high diagnostic accuracy of the test is being evaluated with the dedicated imaging software.