Aim: Saline irrigation is routinely used in the sinonasal cavity for both mucosal lavage and topical medication distribution. Existing commercially available squeeze bottles use 200-240mL of fluid, with a 5mm diameter nozzle, aimed vertically with a 45 degree head angle. Evidence for these variables remains severely limited due to inadequate experimental models (cadaveric, 3-dimensional [3D] printed, imaging of labelled dyes and radioisotopes). We aimed to optimise the design of squeeze bottles, in terms of volume, squeeze force and head angle, using a series of experiments utilising custom-made computer-controlled electronic flow-meters, physical models, computational fluid dynamics (CFD) models and human experiments. METHODS: We present a comprehensive summary of the results of five (5) of our major peer-reviewed publications. Results: Compared with industry standard 200–240 mL squeeze bottles, higher volume irrigation (400 mL) and greater squeeze force (ramp time 0.1 s), along with backward head tilt optimised irrigation coverage and shear force on sinonasal mucosal surfaces. Novel 400mL squeeze bottles were subsequently designed, prototyped and manufactured and are currently undergoing clinical testing. A standardised irrigation “Burst-profile” from the averaged results of 10 human subjects is presented for future studies. Conclusion: Using multiple parametric CFD experiments our saline rinse squeeze bottle design and technique improved sinonasal mucosal coverage (> 3X) and shear force. This technology has the potential to revolutionise the development of novel saline irrigation devices and techniques, with significant translational clinical benefit. Funding: Passe and Williams Foundation Conjoint Grant – Inthavong/Singh, ENT Technologies. Disclosures: A/Prof Narinder Singh is a consultant for ResMed, Optinose, Nasus, GSK and ENT Technologies and receives grant funding from Microsoft, Passe and Williams Foundation, Ramsay Hospital Research Foundation and CRC-P.