Introduction: It is hypothesized that substance use disorder (SUD) has a correlation with attachment style and emotional regulation difficulties. The aim of the current study is to compare attachment style and quality of life (QOL) between patients with SUD and healthy subjects and to explore the role played by attachment style in predicting QOL and readiness to change (RTC) substance use behavior. Materials and Methods: this study is a causal-comparative study where 100 patients with SUD and 100 healthy subjects are selected using multi-stage sampling from August, 2018 to December, 2018 in Zahedan, Iran. The participants are evaluated using the socio-demographic information form, the 36-Item Short-Form Health Survey (SF-36), Adult Attachment Questionnaire (AAQ), and the Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES). Results: there are significant differences between the two groups with regards to mean and standard deviation of QOL and attachment style. There was a negative correlation between the avoidant insecure attachment style and the anxious/ambivalent insecure attachment style, while there was a positive correlation between QOL and RTC among patients with SUD. When controlling for age, gender, and educational level, attachment style was able to predict QOL and RTC among patients. Conclusion: given the role of attachment style in predicting QOL and RTC, these components are considered as potential therapeutic objectives for patients with SUD. Therefore, making use of non-pharmacological approaches may reduce tendency towards substance use, and increase RTC and QOL through improving the attachment style of the individual, thereby reducing his/her negative emotions.