SNIIRAM/SNDS, the French administrative health care database, covers around 99% of the population. Its main limitation is the absence of clinical information and biological results. This report exposes the value of SNIIRAM/SNDS enrichment by external databases, and the linkage issues. It is illustrated by examples: the well-known population-based cohort CONSTANCES created to answer to epidemiological research questions with a specific interest on occupational and social factors, chronic diseases, and aging; the CANARI study, a regional-based study that collected Gleason score in all pathology laboratories in Brittany and then, linked pathology results to an ad hoc extraction from SNIIRAM database; the goal was to investigate the risk of high grade prostate cancer in patients treated by 5-alpha-reductase inhibitors for a symptomatic benign prostatic hyperplasia; the SACHA study, that identified and medically validated major bleeding event referred to emergency wards, then linked those clinical data to SNIIRAM; the goal was to minimize misclassification bias when estimating bleeding risk in patients who were prescribed antithrombotic drugs; the ISO-PSY study linked the SNIIRAM with the national cause of death registry (CépiDc) and the nationwide emergency department surveillance system (OSCOUR^® network) to investigate the potential link between isotretinoin and suicidal risk; the EFEMERIS cohort that assesses drugs prescriptions in French pregnant women who delivered in the Haute-Garonne region; the EPI-GETB-AM study that derived a SNIIRAM/SNDS-based algorithm to identify venous thromboembolism and linked SNIIRAM/SNDS to the EPI-GETBO-III survey for validation. Another perspective of SNDS enrichment is clinical trials’ data for medico-economic assessment, and extended follow-up without attrition bias. Linkage is not straightforward. Apart from regulatory approbation and authorized data center issues, which could be solved by the Health Data Hub Initiative, a multidisciplinary team with medical, pharmacological and methodological knowledge, as well as with technical skills is essential to handle the whole process.