OBJECTIVES: To explore demographic and clinical factors associated with choice of type 2 diabetes mellitus (T2DM) treatment at time of treatment intensifications. METHODS: For T2DM patients from the Netherlands (NL), Italy (IT), Spain (ES) (2007-2011) and United Kingdom (UK) (2008-2012) antidiabetic drug prescription records were obtained from electronic health-care record databases.  Oral monotherapy was defined as first-line, oral dual therapy as second-line, >2 oral treatments or oral combined with an injectable as third-line and injectables only as fourth-line treatment. Treatment intensification was defined as starting a higher line of treatment. General characteristics, comedication, comorbidities and clinical parameters associated with choice of treatment were identified using multivariate logistic regression. RESULTS: From NL, IT, ES and UK 48,479, 67,751, 348,572 and 152,544 T2DM patients were included, respectively. For first-line treatment advanced age and renal comorbidity were associated with SU (all countries), whereas high BMI was inversely associated in UK and ES. For second-line treatment advanced age was associated with biguanide + SU (all countries) and renal comorbidity with SU + dipeptidyl peptidase-4 inhibitors (DPP4) in UK and NL. High BMI was associated with biguanide + thiazolidinedione (TZD) in UK and ES, and with biguanide + DPP4 (UK only). For third-line treatment advanced age and renal comorbidity were associated with SU + insulin in ES and UK, but high BMI was inversely associated with any third-line treatment containing insulin. For fourth-line treatment women were more likely to receive glucagon-like peptide-1 analogs than men in UK and ES. Calendar year and prior treatment played differing roles in treatment choices in different countries. CONCLUSIONS: Age, BMI and renal comorbidity were the predominant factors associated with T2DM treatment choice across treatment intensifications in four EU countries. Associations identified in this explorative study are intended to identify questions for further research.