In a companion paper, we showed how local hospital leaders could assess systems and identify key safety concerns and targets for system improvement. In the present paper, we consider how these leaders might implement practical, low-cost interventions to improve safety. Our focus is on making immediate safety improvements both to directly improve patient care and as a foundation for advancing care in the longer-term. We describe a ‘portfolio’ approach to safety improvement in four broad categories: prioritising critical processes, such as checking drug doses; strengthening the overall system of care, for example, by introducing multiprofessional handovers; control of known risks, such as only using continuous positive airway pressure when appropriate conditions are met; and enhancing detection and response to hazardous situations, such as introducing brief team meetings to identify and respond to immediate threats and challenges. Local clinical leaders and managers face numerous challenges in delivering safe care but, if given sufficient support, they are nevertheless in a position to bring about major improvements. Skills in improving safety and quality should be recognised as equivalent to any other form of (sub)specialty training and as an essential element of any senior clinical or management role. National professional organisations need to promote appropriate education and provide coaching, mentorship and support to local leaders.