Aims: Tobacco smoking is having a far more serious effect on reproductive health than previously thought and is responsible for many thousands of cases of impotence, miscarriages, and infertility each year. Among those experiencing difficulty with conception, a male fertility problem partly resulting from fertility hormone derangements is considered important. This study assessed the effect of cigarette smoking on fertility hormone levels in males. Study Design: This is a cross sectional study. Place and Duration of Study: The study was conducted from January 2010 to November 2010 at the Tamale Teaching Hospital located in the Northern Region of Ghana. Methodology: In this study, a total of 99 subjects were recruited comprising, 54 (54.5%) smokers and 45 (45.5%) non-smokers. The smokers were stratified into mild (smoke 10 sticks/day). Fertility regulating hormones such as follicle stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), testosterone (TES), oestradiol (E2II) and sex hormone binding globulins (SHBG) were assayed. Total protein (TPRO) and albumin (ALB) were also estimated. Results: In this study, 14.1% of the smokers were mild smokers, 30.3% were moderate smokers while 10.1% were heavy smokers. FHS, LH, PRL, E2II, SHBG were not significantly different among smokers and non-smokers; however, testosterone (TES) levels (ng mL-1) in smokers were significantly higher compared to non-smokers (7.33 ± 3.3 vrs 5.78 ± 1.8, p = .01). ALB (g/L) was significantly lower in smokers (35.91 ± 4.5 vrs 41.18 ± 7.5, P = .04) while GLO (g/L) was significantly higher in smokers (44.28 ± 7.7 vrs 34.15 ± 8.6, P = .005) compared to non-smokers. Conclusion: This study therefore concludes that, fertility hormone levels were not significantly affected by tobacco smoking; except testosterone level, which is significantly higher in smokers compared to non-smokers