Poor adherence with pharmacotherapy is well recognised as one of the main barriers to achieving satisfactory blood pressure control, although accurately measuring patient adherence has historically been very challenging. Urine analysis by high-performance liquid chromatography-tandem mass spectrometry has recently become routinely available as a method of screening for non-adherence. In addition to measuring rates of adherence in hypertensive patients, this study aimed to investigate the reasons for non-adherence given by patients and how patients react when they are informed of their results. This was a retrospective observational study looking at results from the routine use of this assay in a specialist hypertension clinic in Birmingham, UK, in patients with uncontrolled hypertension and those under consideration for renal denervation. Out of the 131 patients analysed, only 67 (51%) were taking all their medications as prescribed. Forty-three patients (33%) were taking some of their medications, whilst 21 patients (16%) were completely non-adherent. The most common reasons cited for non-adherence were adverse effects of medication and forgetfulness. Adherence rates for thiazide/thiazide-like diuretics and spironolactone were lower than for other classes of antihypertensive drug. Despite the objective nature and high sensitivity of the test, 36% of non-adherent patients disputed the results. A minority of patients did not attend follow-up. Further research investigating the implications of a ‘non-adherence’ result on the patient-clinician relationship is required.