Background: Angiotensin-converting-enzyme (ACE) inhibitors and b-blockers are standard therapy for chronic heart failure (CHF). b-blockers are recommended to be initiated after ACE-inhibitors, but this order is not evidence based. The initiation order may be important since many, especially elderly CHF patients cannot tolerate target doses of both. Data suggest that b-blockers may be more important to CHF patients than ACE-inhibitors, especially in early stages of CHF. Aims: To compare the effect on combined death or hospitalisation of initial monotherapy with either bisoprolol or enalapril, followed by combination therapy. Methods: One-thousand CHF patients without ACE-inhibitor, b-blocker or angiotensin-receptor-blocker therapy will be randomised 1:1 to monotherapy with either enalapril or bisoprolol for 6 months, followed by combined therapy for 6-18 months. The primary objective is to show non-inferiority for bisoprolol-first vs. enalapril-first regarding combined death or hospitalisation. If that is shown, superiority for bisoprolol-first will be tested. Conclusions: If the trial shows non-inferiority for bisoprolol-first vs. enalaprilfirst, the first CHF therapy may be chosen based on individual judgement in each patient. If bisoprolol-first is superior to enalapril-first, a b-blocker should be given prior to an ACE-inhibitor in CHF, and the paradigm of testing CHF compounds against a background of ACE-inhibitor therapy will be challenged.