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The Directorate’s roots go back to 1983 when, under the name of Health Information Unit (HIU), a small team comprising of two nurses and an Administration​ Officer was set up, primarily to work on the MONICA Survey which was carried out in 1984.  The offices were located in Harper Lane, Floriana. 

In 1985, the entire unit shifted to the new premises in G’Mangia with a substantial increase in staff under the new name "Health Services Information Unit" (HSIU). The first 3 registers started operating under a manual system. These were the Mortality, Cancer and Infectious Diseases registers.  Concurrently, with the help of WHO-Europe, a ‘first generation’ computer mainframe was brought in together with IT-trained personnel in order to create the first 'national health information system', including the first computerised Patient Master Index of the patient files at St Luke’s Hospital.


In 1991, the Directorate was re-christened as the "Health Information Systems Unit" (HISU) to reflect its widening remit with respect to information systems.  In this period the first Windows-based PCs were introduced on which the package DBase III Plus was introduced to facilitate the maintenance of the patient registers.  In 1993 the Directorate was recognised as a Department for the first time under the name 'Department of Health Information' (DHI).  The DHI was the driving force for the introduction of web-based services, with the first health website being launched in 1996.


In 1997 the Directorate moved to its current location.  In this same year, the DHI was the fulcrum for the introduction of the first integrated Patient Administration System (PAS) in Government hospitals.  In 2000, the Directorate went through yet another transformation with increasing demand for most reports to be readily available online on its website.  The year 2001 hailed the return of the health survey function for which the Directorate had been primarily created back in 1983, with the first edition of the National Health Interview Survey (NHIS).  A later edition was carried out, in conjunction with most other EU member states in 2008 as part of the European Health Interview Survey project (EHIS) which has now been implemented across Europe with a second wave conducted between 2013 - 2015.


In 2007, the Directorate changed its name to 'Department of Health Information and Research (DHIR)' to also highlight its now established role in the area of national health surveys. A few years after this the department was recongisned as a directorate and it was designated the name 'Directorate for Health Information and Research' as it is known today.  The changes instated since 2007 were a product of a major audit of the functions of this Directorate. Over the past 30 years the Directorate has grown from simply one maintaining a number of registries to an intelligence hub to aid health authorities in the monitoring of the health of the Maltese population for the design of new strategies and policies.