The long-term acceptability of perindopril in mild-to-moderate chronic heart failure (CHF) was evaluated in a multicenter open study. A total of 320 patients with a mean age of 62 +/- 1 years and CHF of New York Heart Association (NYHA) class I (2 patients), II (204 patients), or III (114 patients) were included after a 2-week run-in period during which time vasodilators were stopped and diuretic and/or digoxin therapy stabilized. Perindopril treatment was started at 2 mg, increasing to 4 mg once daily after 2 weeks if supine systolic blood pressure remained > 100 mm Hg. After this does titration period, follow-up visits were scheduled at monthly intervals for the first 3 months, then at 3-month intervals with a maximum period of follow-up being 30 months. At the time of analysis, mean duration of treatment was 276 days and 208 patients were treated greater-than-or-equal-to 6 months. Of the 320 patients, 10 (3.1%) died, 9 (2.8%) were withdrawn for worsening heart failure, and 38 (11.9%) for nonfatal adverse events, including cough (2.8%), dizziness or orthostatic discomfort (1.9%), angina pectoris (1.6%), and cutaneous signs (1.3%). Exercise test duration increased from 516 +/- 14 to 659 +/- 19 sec after 6 months of treatment (p < 0.01). At 6 months, 55.6% of patients improved by at least 1 NYHA class. Supine systolic blood pressure decreased slightly from 137 +/- 2 to 132 +/- 1 mm Hg (p < 0.01) and plasma creatinine levels remained stable from 100 +/- 2 to 102 +/- 2 mumol/liter after 6 months of treatment. Similar results were observed in 105 patients treated for 12 months and 30 patients for 30 months. Overall, 97 patients (30.3%) reported symptoms during the study, including persistent cough (6.3%), dizziness (4.1%), asthenia (4.1%), cutaneous signs (3.1%), headache (2.5%), and angina pectoris (2.5%). These results show the good acceptability of perindopril in the long-term treatment of mild-to-moderate CHF with a low incidence of complaints by patients and no significant change in renal function.