Although gender differences in morbidity and mortality have been measured in patients with moderate to severe burn injury, little attention has been directed at gender effects on health-related quality of life (HRQoL) following burn injury. The current study was therefore conducted to prospectively measure changes in HRQoL for males and females in a sample of burn patients.A total of 114 adults who received treatment at a statewide burns service for a sustained burns injury participated in this study. Instruments measuring generic health status (Short Form 36 Medical Outcomes Survey version 2), burn-specific HRQoL (Burns Specific Health Scale-Brief), psychological distress (Kessler Psychological Distress Scale) and alcohol use (Alcohol Use Disorders Identification Tool) were prospectively measured at 3, 6 and 12 months post-burn.In the 12 months post-injury, female patients showed overall poorer physical (p=0.01) and mental health status (p<0.001), greater psychological distress (p<0.001), and greater difficulty with aspects of burn-specific HRQoL: body image (p<0.001), affect (p<0.001), interpersonal functioning (p=0.005), heat sensitivity (p=0.01) and treatment regime (p=0.01). While significant interaction effects suggested that female patients had more improvement in difficulties with treatment regime (p=0.007), female patients continued to report greater difficulty with multiple aspects of physical and psychosocial health status 12 months post-injury.Even though demographic variables, injury characteristics and burn care interventions were similar across genders, following burn injury female patients reported greater impairments in generic and burn-specific HRQoL along with psychological morbidity, when compared to male patients. Urgent clinical and research attention utilising an evidence-based research framework, which incorporates the use of larger sample sizes, the use of validated instruments to measure appropriate outcomes, and a commitment to monitoring long-term care, can only improve burn-care.