The efficacy of the Crataegus preparation Cralonin was tested for non-inferiority to standard treatment for mild cardiac insufficiency in a multicentre non-randomised cohort study in patients with congestive heart failure of New York Heart Association class II. Patients received Cralonin (n = 110) or angiotensin-converting enzyme (ACE) inhibitor/diuretics (n = 102) for 8 weeks. To adjust for confounding by baseline factors, populations were stratified according to propensity score. After adjusting, there were no statistically significant differences between treatment groups. Treatment efficacy was assessed on 15 variables. A stringent non-inferiority criterion for the upper limit of the 97.5% one-sided CI of the treatment difference was set to 0.2× the SD. Both treatment regimens improved scores on most variables studied, with the greatest effect on double product after exercise (average score reduction 15.4% with Cralonin vs. 16.0% for the control group). Non-inferiority of Cralonin was demonstrated on seven variables. Both treatments were well tolerated.