Background Timely progress with attaining benefits from Health Information Technology (HIT) investments requires UK policymakers and others to negotiate challenges in developing structures and processes to catalyse the trustworthy secondary uses of HIT-derived data. Aims We aimed to uncover expert insights into perceived barriers and facilitators for maximising safe and secure secondary uses of HIT-derived data in the UK. Methods We purposively selected individuals from a range of disciplines in the UK and abroad to participate in a thematically analysed, semi-structured interview study. Results We identified a main theme of 'tightrope walking' from our interviews (n = 23), reflecting trying to balance different stakeholders' views and priorities, with sub-themes of 'a culture of caution', 'fuzzy boundaries' and 'cultivating the ground'. The public interest concept was fundamental to interviewees' support for secondary uses of HIT-derived data. Small scale and prior collaborative relationships facilitated progress. Involving commercial companies, improving data quality, achieving proportionate governance and capacity building remained challenges. Conclusions One challenge will be scaling up data linkage successes more evident internationally with regional population datasets. Within the UK, devolved nations have the advantage that 'small scale' encompasses national datasets. Proportionate governance principles developed in Scotland could be more widely applicable, while lessons on public engagement might be learned from Western Australia. A UK policy focus now should be on expediting large-scale demonstrator projects and effectively communicating their findings and impact. Progress could be jeopardised if national data protection laws were superseded by any Europen Union-wide regulation governing personal data.