Aims: To assess long-term prognosis in patients with functional mitral regurgitation (FMR) and left ventricular (LV) dysfunction, receiving current standard pharmacological therapy. Methods and results: We prospectively enrolled 404 consecutive patients (mean age 70.2 ± 10 years) with ischaemic (76.5%) and non-ischaemic (23.5%) LV dysfunction (ejection fraction 34.4 ± 10.8%) and at least mild MR. Results are reported at 4 years’ follow-up. Survival free of all-cause mortality was 53% and cardiac death was 74%. Survival free of all-cause mortality was 50% (95% CI 35–72) for patients with moderate MR, 49% (95% CI 27–65) for severe MR, and 64% (95% CI 47–78) for mild MR (P = 0.03). Survival free of cardiac death was 57% (95% CI 38–74) for patients with moderate MR, 55% (95% CI 30–77) for severe MR, and 94% (95% CI 59–98) for mild MR (P = 0.003). Moderate-to-severe MR [relative risk (RR) 2.7, 95% CI 1.2–6.1, P = 0.003] was an independent predictor of cardiac death but not of all-cause mortality. Survival free of heart failure (HF) was 32%. Survival free of HF was 20% (95% CI 17–35) for patients with moderate MR, 18% (95% CI 15–32) for severe MR, and 62% (95% CI 45–72) for mild MR (P = 0.0001). Moderate-to-severe MR (RR 3.2, 95% CI 1.9–5.2, P = 0.0001) was an independent predictor of HF. Conclusion: The mortality and morbidity of patients with LV dysfunction and FMR remain high despite current standard pharmacological therapy. Moderate-to-severe MR is an independent predictor of cardiac death and HF.