Regional analgesia, opioids, and several oral analgesics are commonly used for the treatment of acute pain after breast cancer surgery. While all of these treatments can suppress the acute postsurgical pain, there is growing evidence that suggests that the postsurgical comorbidity will differ in accordance with the type of analgesic used during the surgery. Our current study reviewed the effect of analgesics used for acute pain treatments on the major comorbidities that occur after breast cancer surgery. A considerable number of clinical studies have been performed to investigate the relationship between the acute analgesic regimen and common comorbidities, including inadequate quality of recovery after the surgery, persistent postsurgical pain, and cancer recurrence. Previous studies have shown that the choice of the analgesic modality does affect the postsurgical comorbidity. In general, the use of regional analgesics has a beneficial effect on the occurrence of comorbidity. In order to determine the best analgesic choice after breast cancer surgery, prospective studies that are based on a clear definition of the comorbidity state will need to be undertaken in the future.