Background: Since prostate-specific antigen (PSA) levels can be influenced by some routinely available clinical factors, a retrospective study was conducted to explore the influence of obesity, smoking habit, heavy drinking and chronic obstructive pulmonary disease on PSA levels in men with histologically confirmed prostate cancer. Patients & methods: We reviewed the medical records of 833 prostate cancer patients undergoing radical prostatectomy. Results: Serum PSA levels at the time of surgery were not associated with either BMI or history of chronic obstructive pulmonary disease or heavy drinking. Conversely, PSA levels were associated with smoking status. Conclusion: Among the clinical factors explored in this homogeneous population, only tobacco use was associated with PSA levels, which should be considered when using PSA-based screening in male smokers.