OBJECTIVES To describe current disease-modifying antirheumatic drugs (DMARDs) prescription in rheumatoid arthritis (RA) with reference to best practice and to identify temporal and regional trends in the UK. DESIGN Descriptive, register-based cohort study. PARTICIPANTS Permanently registered patients aged ≥18 years with a recorded diagnosis of RA between 1 January 1995 and 31 March 2010 and matched controls. Participants with RA were identified through screening of all patients in the General Practice Research Database (GPRD) with a clinical or referral record for RA and at least 1 day of follow-up. SETTING 639 general practices in the UK supplying data to the GPRD. MAIN OUTCOME MEASURES Medication prescribing between 3 and 12 months of RA diagnosis by region and time period (1995-1999, 2000-2005 and 2006-April 2010). RESULTS Of the 35 911 patients in the full RA cohort, 15 259 patients (42%) had incident RA. Analysis of prescribing in incident RA patients demonstrated that between 1995 (baseline) and 2010 there was a substantial increase in DMARD, and specifically methotrexate, prescribing across all regions with a less marked increase in combination DMARD prescribing. Taking 12-month prescribing as a snapshot: DMARD prescribing was 19-49% at baseline increasing to 45-74% by 2006-April 2010; methotrexate prescribing was 4-16% at baseline increasing to 32-60%; combination DMARD prescribing was 0-8% at baseline increasing to 3-17%. However, there was marked regional variation in the proportion of RA patients receiving DMARD regardless of time period. CONCLUSIONS There has been a substantial increase in prescribing of DMARDs for RA since 1995; however, regional variation persists across the UK with relative undertreatment, according to established best practice. Improved implementation of evidence-based best clinical practice to facilitate removal of treatment variation is warranted. This may occur as a result of the implementation of published national guidance.