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Aim To examine hepatic enzyme test results throughout the course of pregnancy in women maintained on methadone or buprenorphine. Design Participants were randomized to either methadone or buprenorphine maintenance. Blood chemistry tests, including liver transaminases and hepatitis C virus (HCV) status, were determined every 4 weeks and once postpartum. As part of a planned secondary analysis, generalized mixed linear models were conducted with aspartate aminotransferase (AST), alanine aminotransferase (ALT) and gamma-glutamyl transferase (GGT) as the dependent variables. Setting Six US sites and one European site that provided comprehensive treatment to pregnant opioid-dependent women. Participants A total of 175 opioid-dependent pregnant women enrolled in the Maternal Opioid Treatment: Human Experimental Research (MOTHER) study. Findings ALT, AST and GGT levels decreased for all subjects across pregnancy trimesters, rising slightly postpartum. HCV-positive subjects exhibited higher transaminases at all time-points compared to HCV-negative subjects, regardless of medication (all Ps<0.05) condition. Both HCV-positive and negative buprenorphine-maintained participants exhibited lower GGT levels than those who were methadone-maintained (P<0.05). Conclusions Neither methadone nor buprenorphine appear to have adverse hepatic effects in the treatment of pregnant opioid-dependent women