Purpose/Objective: The present study examines associations between levels of limb loss (partial hand vs. higher levels of limb loss) and eight clinically relevant measures of functional impairment, psychological well-being, and substance use. Research Method/Design: A cross-sectional, multisite study conducted at seven prosthetic rehabilitation centers across the United States. A total of 305 participants with upper limb loss (Mage = 44.28, SD = 15.45; 68.5% male; 70.5% white) completed orally administered self-assessments of pain interference, perceived activity restrictions, posttraumatic stress disorder (PTSD), depression, emotional reaction to their physical condition, problematic alcohol use, prescription medication overuse, and illicit drug use. Results: Results showed individuals with partial hand loss were at significantly greater odds of endorsing pain interference and screening positive for PTSD. Results also showed level of limb loss was significantly associated with emotional reaction to their physical condition, such that participants with partial hand loss scored significantly above those with higher level limb loss. Conclusions/Implication: The current study highlights level of limb loss as an important correlate of several functional impairments and psychological measures among individuals with upper limb loss. These findings may inform clinicians and occupational therapists in their development of treatment and rehabilitation. In particular, practitioners should be cognizant of their patient’s level of limb loss, as individuals with partial hand loss may be more susceptible to greater emotional reactions to their physical condition and increased psychological distress due to pain interfering with their work and elevated posttraumatic stress symptoms.