Recent studies reported symptomatic overlap between attention deficit/hyperactivity disorder (ADHD) and borderline personality disorder (BPD). Methylphenidate (MPH) is the most efficient treatment for ADHD. We assessed the efficacy and tolerability of MPH treatment in adolescent females who met the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria for both disorders. Fourteen BPD/ADHD female adolescents aged 14–19 years were treated with MPH for 12 weeks, targeting ADHD, BPD symptoms, and aggressive behavior, as rated by ADHD-rating scale (ADHD-RS) and Clinical Global Impression-Severity (CGI-S) scale for BPD and aggressive behavior severity. A significant improvement was detected in both ADHD and BPD severity (baseline vs. end point, ADHD-RS: 33.1±4.8 vs. 17.6±5.2, P<0.001; BPD CGI-S: 4.6±0.8 vs. 3.4±0.8, P<0.0005, respectively) as well as in aggressive behavior (Aggression CGI-S: 3.5±1.3 vs. 1.8±0.5, P<0.001). MPH was well tolerated. MPH may be useful and well tolerated in treating some shared symptoms of ADHD and BPD among female adolescents. Controlled studies are needed to substantiate these findings.