[Objective] To investigate the median and long-term follow-up effect of the therapy of long-segment lumbar fusion on lumbar spinal stenosis patients with severe medical diseases. [Methods] A retrospective analysis was performed on 176 patients aged 65 years or older who underwent 2-level or above lumbar fusion from January 2008 to September 2017 (were followed up for more than 2 years). According to the classification of the American Society of Anesthesiologists (ASA) score, the patients were divided into two groups: group low ASA (ASA grade 1 and 2) with 105 cases and group high ASA (ASA grade 3 and 4) with 71 cases. Clinical and imaging data were compared between the two groups. [Results] The operation of all patients were completed successfully, and there were no perioperative deaths. The follow-up time was 24~138 months, with an average of 56.81±25.16 months. VAS and ODI scores in the last follow-up were significantly lower than that of pre-operation (P<0.01). There was no statistical significance in VAS score, ODI score, intervertebral fusion rate and treatment satisfaction between preoperative and postoperative follow-up in two groups (P>0.05). The operative time, intraoperative blood loss, length of in group high ASA were all higher than those in group low ASA, but the differences were not statistically significant (P>0.05). The incidence of perioperative complications in group high ASA was significantly higher than that in group low ASA (P<0.05). The incidence of complications during follow-up was higher in group high ASA than that in group low ASA, but the difference was not statistically significant (P>0.05). [Conclusion] On the basis of active control of combined medical diseases, lumbar spinal fusion surgery is effective and safe in senile degenerative LSS patients with severe medical diseases.