Background Addressing the problem of preventable drug related morbidity (PDRM) in primary care is a challenge for health care systems internationally. The increasing implementation of clinical information systems in the UK and internationally provide new opportunities to systematically identify patients at risk of PDRM for targeted medication review. The objectives of this study were (1) to develop a set of explicit medication assessment criteria to identify patients with sub-optimally effective or high-risk medication use from electronic medical records and (2) to identify medication use topics that are perceived by UK primary care clinicians to be priorities for quality and safety improvement initiatives. Methods For objective (1), a 2-round consensus process based on the RAND/UCLA Appropriateness Method (RAM) was conducted, in which candidate criteria were identified from the literature and scored by a panel of 10 experts for 'appropriateness' and 'necessity'. A set of final criteria was generated from candidates accepted at each level. For objective (2), thematically related final criteria were clustered into 'topics', from which a panel of 26 UK primary care clinicians identified priorities for quality improvement in a 2-round Delphi exercise. Results (1) The RAM process yielded a final set of 176 medication assessment criteria organised under the domains 'quality' and 'safety', each classified as targeting 'appropriate/necessary to do' (quality) or 'inappropriate/necessary to avoid' (safety) medication use. Fifty-two final 'quality' assessment criteria target patients with unmet indications, sub-optimal selection or intensity of beneficial drug treatments. A total of 124 'safety' assessment criteria target patients with unmet needs for risk-mitigating agents, high-risk drug selection, excessive dose or duration, inconsistent monitoring or dosing instructions. (2) The UK Delphi panel identified 11 (23%) of 47 scored topics as 'high priority' for quality improvement initiatives in primary care. Conclusions The developed criteria set complements existing medication assessment instruments in that it is not limited to the elderly, can be implemented in electronic data sets and focuses on drug groups and conditions implicated in common and/or severe PDRM in primary care. Identified priorities for quality and safety improvement can guide the selection of targets for initiatives to address the PDRM problem in primary care.