Dosing of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in patients with heart failure (HF) treated with cardiac resynchronization therapy (CRT) may affect long-term outcomes. Retrospective data were collected at baseline and follow-up for consecutive patients who had CRT implanted and attended the institutional specialist HF pacing clinic. The study end point was death from any cause or hospitalization for worsening HF 24 months after implantation. Ninety-one patients (72 men, 68 ± 12 years old) with decreased left ventricular ejection fraction (24 ± 6%) were included. At baseline 85 patients (93%) were on ACE inhibitors/ARBs. At 6 months 3 patients had died and 86 of 88 (98%) were on ACE inhibitors/ARBs. Doses were uptitrated from 55 ± 35% of target dose (TD) at baseline to 62 ± 31% TD at month 6 (p = 0.018), whereas blood pressure was unchanged. Patients treated with <50% TD of ACE inhibitors/ARBs (n = 20) at month 6 had worse 24-month event-free survival than those on 50% to 99% TD (n = 38, p = 0.011, log-rank test) or ≥100% TD (n = 30, p = 0.007, log-rank test). Failure to achieve a dose ≥50% TD of ACE inhibitors/ARBs at 6 months after CRT implantation was an independent predictor of all-cause mortality or hospitalization (hazard ratio 3.99, 95% confidence interval 1.66 to 9.62, p = 0.002) after adjustment for potential confounders including age, estimated glomerular filtration rate, diabetes and New York Heart Association class. In conclusion optimal dosing of ACE inhibitors/ARBs is an independent predictor of prognosis in patients with HF treated with CRT and it can be achieved by a structured follow-up within a specialized HF pacing clinic.