Context: Attainment of safe GH and IGF-1 levels is a central goal of acromegaly management. Objective: The aim of this study was to determine the extent to which reductions in GH and IGF-1 concentrations correlate with amelioration of radiological, metabolic, vascular, cardiac, and respiratory sequelae in a single unselected patient cohort. Study Design: This was a prospective, within-subject comparison in 30 patients with newly diagnosed acromegaly (15 women and 15 men: mean age, 54.3 years; range, 23-78 years) before and after 24 weeks of lanreotide Autogel (ATG) therapy. Results: Reductions in GH and IGF-1 concentrations and tumor volume were observed in all but 2 patients (median changes[δ]:GH,-6.88 μg/L [interquartile range -16.78 to-3.32, P=.000001]; IGF-1, -1.95 × upper limit of normal [-3.06 to -1.12, P=.000002]; and pituitary tumor volume, -256mm3 [-558 to -72.5, P=.0002]). However, apnea/hypopnea index scores showed highly variable responses (P = .11), which were independent of δGH or δIGF-1, but moderately correlated with δweight (R2 = 0.42, P = .0001). Although systolic (P = .33) and diastolic (P = .76) blood pressure were unchanged, improvements in arterial stiffness (aortic pulse wave velocity, -0.4 m/s [-1.2 to -0.2, P = .046]) and endothelial function (flow mediated dilatation, -1.73% [-0.32 to -6.19, P = .0013]) were observed. Left ventricularmassindex regressed in men (-11.8g/cm2 [-26.6 to -1.75], P=.019) but not inwomen (P = .98). Vascular and cardiac changes were independent of δGH or δIGF-1 and also showed considerable interindividual variation. Metabolic parameters were largely unchanged. Conclusions: Presurgical ATG therapy lowers GH and IGF-1 concentrations, induces tumor shrinkage, and ameliorates/reverses cardiac, vascular, and sleep complications in many patients with acromegaly. However, responses vary considerably between individuals, and attainment of biochemical control cannot be assumed to equate to universal complication control.