Background Despite effective treatments, blood pressure (BP) control remains suboptimal. Objective The SIMPLIFY study aimed at identifying key factors related to therapeutic inertia in Belgium and Luxembourg, and evaluating how uncontrolled treated hypertension is managed in primary care. Methods In a 2017 cross-sectional survey, 245 general practitioners (GP) collected routine clinical data from 1,852 consecutive uncontrolled (Office SBP/DBP [greater than or equal to] 140/90 mmHg) hypertensive adult patients taking at least one antihypertensive drug. Results Patients were 64 years old on average, 48% were women, 61% had dyslipidemia, 33% had diabetes mellitus and 22% had established cardiovascular disease. Half of the patients had 2 or more comorbidities. Patients had been treated for hypertension for an average period of 8 years, 40% of patients were in hypertensive stages 2-3, 44% were treated with monotherapy only, 28% with free combinations and 28% with at least one single pill combination (SPC). Therapeutic adherence was rated as 'good' in 62% of patients. AHT treatment was modified in 84% of patients. In the group of patients with stage 2-3 hypertension, treatment remained unchanged in 5%. In the group of patients with stage 1 hypertension, treatment remained unchanged in 23% of patients. Patients treated for longer than 10 years were less likely to undergo treatment change (81%) compared to patients treated for less than 10 years (87%). Patients with 1 or 2 comorbidities were more likely to have their treatment modified (87%) compared to those with no comorbidities (61%) and those with [greater than or equal to] 3 comorbidities (79%). If treatment was modified, a SPC was introduced in 90% of cases; 91% in stage 1-2 hypertension and 84% in stage 3 hypertension. SPCs were less frequently initiated in patients without comorbidities. Main reasons for the GPs to switch from a free association towards SPC were 'better BP control' (55%), 'better therapeutic compliance' (53%) and 'simplicity for the patient' (50%). Conclusion The SIMPLIFY study confirms therapeutic inertia in hypertension management. After an average of 8 years hypertension treatment, almost 1 in 2 uncontrolled treated patients are on monotherapy. The key inertia drivers seem to be age, mild grade hypertension, isolated systolic hypertension, longer duration of antihypertensive treatment and better therapeutic adherence. When treatment is updated by the GP, the currently preferred strategy is switching towards SPC based therapy to improve BP control, and enhance therapeutic compliance by simplifying treatment for the patient. Trial registration pharma.be visa number: VI 17/01/20/01 ISRCTN registered study: ISRCTN16199080.