Objective To investigate the clinical features of isolated systolic hypertension (ISH) in very elderly patients and their condition after drug therapy. Methods Clinical data of 403 very elderly hospitalized patients (≥ 80 years old) suffering from ISH in our hospital from January 2008 to October 2009 were collected. All of them were followed up for duration of 5 years. Their basic data, incidences of hypertensive and cardiovascular complications, the usage of antihypertensive drugs, including calcium channel blocker (CCB), angiotensin-converting enzyme inhibitor (ACEI), angiotensin Ⅱ-receptors antagonist (ARB), β-receptor blocker, diuretics, α-receptor blocker, and nitrates were analyzed. Results Among the 403 patients, 83 patients (20.6%) were grade Ⅰ hypertension, 216 (53.5%) grade Ⅱ hypertension, and 104 (25.8%) grade Ⅲ hypertension. There were 375 cases (93.1%) having complications before treatment, and 397 cases (98.5%) after 5 years’ treatment. The patients with systolic blood pressure (SBP) above 150mmHg and diastolic blood pressure (DBP) below 60mmHg had the highest incidences of complications. No matter the patients were divided according to their age or blood pressure, the blood pressure was well-controlled. The rate of well-controlled blood pressure was 83.9% after 12 weeks’ treatment, and 84.4% in 5 years later, both with significant difference when compared with the pressure before treatment (SBP, P＜0.01; DBP, P＜0.05). There were 135 cases having SBP below 140mmHg, and 55 cases having DBP below 60mmHg. CCB was most commonly used antihypertensive drug (n＝182), followed by β-receptor blocker (n＝179), diuretics (n＝167), nitrates (n＝132), ACEI (n＝112), ARB (n＝112), and α-receptor blocker (n＝5) sequentially. Most of the patients used more than 1 kind of antihypertensive drugs (329, 81.6%). Among them, those took combination of 4 kinds were the least (53, 13.2%), and those administered combination of 2 kinds was the most (180, 44.7%). Only 74 patients (18.4%) used only 1 kind of antihypertensive drug. Conclusion It is quite common for the very elderly ISH patients to have complications. In clinical practice, antihypertensive drug should be selected according to the patient’s condition, and individualized therapy needs to be designed based on blood pressure and comorbidities. Most of the patients need combination of different drugs. During the treatment, clinician should control not only SBP, but also DBP. DBP below 60mmHg might increase the incidence of cardiovascular complications.