Although no psychotropic agents are specifically licensed for the management of borderline personality disorder (BPD), pharmacological treatment appears to be common. This study aimed to examine the drug prescriptions for patients with BPD in clinical practice, analyze the prescription patterns from the appearance of the American Psychiatric Association guidelines in 2001 until the National Institute for Health and Clinical Excellence guidelines in 2009, and identify the factors associated with such prescription of each type of drug. Naturalistic study on 226 consecutive BPD patients admitted to an outpatient BPD program. Socio-demographic, clinical and pharmacological treatment information was collected; factors associated with drug prescription were examined using logistic regression analyses for dichotomous outcomes measures. Changes in prescription patterns over time were also evaluated. Patients received an average of 2.7 drugs; only 6% were drug-free; 56% were taking ≥3 drugs and 30% ≥4 drugs. Over the past 8 years, prescription of antidepressants has remained stable; there has been a significant reduction in prescription of benzodiazepines and an increase in the use of mood stabilizers and atypical antipsychotics. Comorbidity with Axis I disorders was the main factor associated with drug prescription. Drug prescription and polypharmacy are common in the management of BPD in clinical practice.