Background/Purpose Existing research from developing countries indicate a connection between substance use and mental health status among adolescents. However, there is dearth of studies examining substance use, especially alcohol, and its relationship to mental health among African adolescents. This study examines the latter relationship among Ghanaian high school adolescents. Method Data from the 2008 Ghana Global School-based Student Health Survey (GSHS) were utilized. Analysis included prevalence estimates and complex sample logistic regression to examine relationships between current drinking and the following; loneliness, anxiety, signs and symptoms of depression, suicide ideation, and suicide planning. Gender, parental alcohol use, and parental understanding of adolescent's problems were controlled for in the analysis. Analysis/Results 15.3% of students were classified as current drinkers. When controlling for gender, parental alcohol use, and parental understanding of adolescent's problems, students classified as current drinkers were 1.4 (95% CI: 1.1, 1.8) times more likely to report anxiety, 1.6 (95% CI: 1.3, 1.9) times more likely to report signs and symptoms of depression, 1.6 (95% CI: 1.3, 1.9) times more likely to report suicide ideation, and 1.7 (95% CI: 1.22, 1.79) times more likely to report making a suicide plan in preceding 12 months compared to students classified as non-drinkers. Conclusions The cross-sectional nature of the survey precludes assessment of directionality of relationship. However, the significant association between alcohol use and mental health indicates the need to simultaneously examine mental health factors when addressing alcohol use among Ghanaian youth.