Background <p>A proportion of clinical trials terminate prematurely, due to logistical or conduct issues and emerging scientific data. Due to a paucity of literature and non-standardised reporting, the rate for all trials is unknown, and little is known about the number and experience of healthcare professionals managing this situation. This study aimed to identify how many UK healthcare professionals delivering clinical research have experienced premature trial termination<b>,</b> the challenges experienced and resources available for managing this situation.</p> Methods <p>Following ethics approval, a national e-survey of self-identifying healthcare professionals delivering clinical research was conducted (April–September 2022). Analysis included descriptive statistics and content analysis for categorization of challenges.</p> Results <p>A total of 65% (<i>n</i> = 89) of healthcare professionals had experienced ≥ 1 premature trial termination. Challenges included communicating with research participants and/or families (<i>n</i> = 20) and emotional distress for participants and/or families (<i>n</i> = 21). Forty-eight healthcare professionals identified resources; of those available for review, one resource provided guidance relating to research participants.</p> Conclusion <p>Premature clinical trial termination creates challenges for care delivery and impacts on participants and/or families. Healthcare professionals need preparation and training to ensure participants are appropriately supported if their trial prematurely terminates.</p>