Memory function is largely mediated by the medial temporal lobe (MTL), and its compromise has been observed in alcohol dependence and chronic cigarette smoking. The effects of heavy alcohol consumption and chronic smoking on hippocampal volumes and MTL metabolites and their recovery during abstinence from alcohol have not been assessed. Male alcoholics in treatment (ALC) [13 smokers (sALC) and 11 non-smokers (nsALC)] underwent quantitative magnetic resonance imaging and short-echo proton magnetic resonance spectroscopic imaging at 1 week and 1 month of sobriety. Outcome measures were compared with 14 age-matched, non-smoking light-drinkers and were related to visuospatial learning and memory. Over 1 month of abstinence, N-acetyl-aspartate, a neuronal marker, and membrane-associated choline-containing metabolites normalized in the MTL of nsALC subjects, but remained low in the MTL of sALC subjects. Metabolite concentration changes in both groups were associated with improvements in visuospatial memory. Hippocampal volumes increased in both groups during abstinence, but increasing volumes correlated with visuospatial memory improvements only in nsALC subjects. In summary, chronic cigarette smoking in alcohol-dependent men appears to have adverse effects on MTL metabolite recovery during short-term sobriety. These data may also have implications for other conditions with established MTL involvement and significant smoking co-morbidity, such as schizophrenia-spectrum and mood disorders.