Erythema nodosum leprosum (ENL) is a multisystem reaction which affects some people with multibacillary (MB) leprosy, but more specifically those with BL or LL type leprosy. The symptoms of ENL can lead to long term physical, social and economic losses, although very little is known about the effect of ENL on quality of life. Methods: A cross-sectional study was conducted in northwest Bangladesh. A Bengali version of the RAND 36-Item Health Survey 1·0 (SF-36) was administered to people under treatment for ENL (n ¼ 29) and controls affected by MB leprosy (n ¼ 46) matched for: sex, treatment status, age, Disability grade at diagnosis, education level and housing type. Chi Square and Wilcoxon RST were used to analyse the data using the R statistical package. Results: Patients with ENL had significantly (P , ·001) worse Health Related Quality of life (HRQoL) scores on all eight SF-36 health concepts: physical functioning, pain, role limitations due to physical and emotional limitations, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Cohen’s d indicated a large effect (d ¼ ·96 to 1·67). The results are compared with results of other published works which examined similar populations Conclusion: HRQoL is significantly impaired in Bangladeshi people suffering from ENL compared with people with MB leprosy and no ENL. ENL affects all areas of a person’s HRQoL measured by the SF-36. Health care providers need to spend time addressing other aspects of a person’s life and not just the physical symptoms.