Objective To investigate the changes of serum markers of cardiovascular disease risk in patients with acromegaly and the effect of six months of treatment with long-acting octreotide on them. Methods The clinical data of 63 patients with acromegaly (acromegaly group) and 69 healthy people (control group) treated in the First Affiliated Hospital of Chongqing Medical University from May 2012 to January 2021 were collected and analyzed retrospectively. According to the blood glucose level, the patients with acromegaly were divided into three subgroups: normal glucose metabolism (NGT) group (n=25), Impaired glucose regulation (IGR) group (n=11) and diabetes mellitus (DM) group (n=27). The age, body mass index (BMI), blood pressure, growth hormone (GH), blood glucose, blood lipid, high-sensitivity C-reactive protein (hs-CRP), fibrinogen and plasma atherogenic index(AIP) between acromegaly group and control group and three glucose metabolism subgroups were compared, and the relationship between age, BMI, blood pressure, fibrinogen, hs-CRP, blood lipid and AIP was analyzed by Spearman correlation analysis.In addition, 16 of 63 patients with acromegaly who finally completed 6-month long-acting octreotide treatment were studied longitudinally, and the changes of the indexes above were compared before and after treatment. Results Compared with the control group, the levels of BMI, blood pressure, fibrinogen, fasting blood glucose (FPG), triglyceride (TG), lipoprotein a [Lp (a)]and AIP were significantly higher, and of hs-CRP, high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C) were significantly lower (P<0.05) in acromegaly group. For subgroup analysis, the TG level was significantly higher in DM group than that in IGR group and NGT group (P<0.05), while the difference between IGR group and NGT group was not statistically significant; The AIP level was significantly higher in DM group than that in NGT group (P<0.05), and no significant difference existed among the other groups. In correlation analysis, AIP was positively correlated with BMI, fibrinogen, FPG, TG, apolipoprotein B (Apo B), non-high density lipoprotein cholesterol (Non-HDL-C), TC/HDL-C, LDL-C/HDL-C, APO B/APO A-1, and Non-HDL-C/HDL-C, but negatively correlated with HDL-C and apolipoprotein A-1 (Apo A-1). After subgroup analysis, AIP was still correlated with the indexes mentioned above, and the difference was statistically significant (P<0.05). The levels of TG and AIP decreased significantly, but of hs-CRP increased significantly (P<0.05) in patients with acromegaly after 6 months of long-acting octreotide treatment compared with that before treatment. Conclusions The cardiovascular risk of patients with acromegaly is increased. Long acting octreotide treatment can reduce the risk of cardiovascular disease in patients with acromegaly.