The purpose of this study is to evaluate long-term results in acromegaly patients who received surgery as first-line treatment. Repeated surgery, radiation therapy and medical treatment were considered in patients showing no postoperative remission or who suffered a relapse. Thirty-five patients suffering from acromegaly were operated on between 1993 and 2009. The patients with persistent hypersecretion received a new surgery when postoperative imaging showed localized residual lesion. The other cases with persistent hypersecretion were treated medically using dopamine agonists, somatostatin analogs or pegvisomant according to the efficiency obtained. Radiotherapy was considered when medical treatment failed to normalize hormonal hypersecretion. The overall remission rate with surgery alone was 57 % (20/35):84 % (16/19) with non-invasive adenomas and 25 % (4/16) with invasive adenomas. Fifteen patients showing no remission after surgery received additional medical and/or radiation therapy resulting in hormonal control in ten of them. Recurrences after initial postoperative remission were observed in six patients who were controlled with subsequent therapy. Using a multimodal treatment approach, the disease was brought under control in 86 % (30/35) of acromegaly patients. Surgery alone produced satisfactory initial results in non-invasive adenomas, but additional treatments were required for most of the invasive lesions.