Background <p>Upper extremity amputations are associated with developing psychiatric conditions. The aim of this study is to identify differences in mental health outcomes for patients undergoing major versus minor upper extremity amputations.</p> Methods <p>Data were obtained from the PearlDiver database between 2010 and 2022 using Current Procedural Terminology and International Classification of Diseases codes. Patients aged 10 and above without prior mental health diagnoses or antidepressant prescription records who underwent upper extremity amputations were stratified by major (shoulder disarticulation, arm, forearm, wrist, transmetacarpal) versus minor (single metacarpal, digit, phalanx) amputations. Demographic characteristics and rates of mental health diagnoses, antidepressant prescriptions, and psychotherapy care were assessed for 90 days and one year postoperatively, using Welch’s T-tests and Pearson’s chi-squared tests.</p> Results <p>Patients with major amputations had increased risk of mental health diagnoses at 90 days (OR: 3.29, <i>p</i> &lt; 0.001) and at one year (OR: 2.01, <i>p</i> &lt; 0.001). Both groups had higher rates of mental health diagnoses than the general population. Patients undergoing major amputations had higher odds of starting antidepressants at 90 days (OR 3.82, <i>p</i> &lt; 0.001) and at one year (OR 2.38, <i>p</i> &lt; 0.001). Psychotherapy care was significantly increased after major amputations at 90 days (OR 5.47, <i>p</i> &lt; 0.001) and at one year (OR 4.18, <i>p</i> &lt; 0.001).</p> Conclusions <p>Mental health disorders, antidepressant use, and psychotherapy care are significantly higher for major upper extremity amputations compared to minor amputations. Surgical teams should provide mental health resources to mitigate negative effects from mental health needs after upper extremity amputation.</p> Level of evidence <p>III.</p>