The shisha is a water pipe used to pass charcoal heated air through a flavored tobacco mixture.(1) Objectives: To determine the association between various psycho-social factors and shisha smoking among medical students aged 18 - 26 years living in Lahore during one year. Design: Case - control study. Place and Duration: King Edward Medical University. From Jan 2012 to Dec 2012. Subjects and Methods: A case - control study with 1:1 case to control ratio was conducted. A total of 100 persons (50 cases and 50 controls) were recruited in the study. Selection was made on laid down criteria from the students of King Edward Medical University, Lahore after taking due consent.Interviews were conducted through a pretested questionnaire. Data was collected, compiled and analyzed through SPSS version 20. Results: All subjects were students of age 18 - 25 years. A total of 100 persons (50 cases and 50 controls) were recruited in the study. Shisha smoking was more prevalent in age group 18 - 22 years (67%), all were unmarried (100%). In bivariate analysis, shisha smoking in males was found to be significantly associated with fashion/social influence (OR: 103.5, 95% CI: 26.103 - 410.379), economic stress (OR: 2.875, 95% CI: 0.837 - 9.881), parental smoking (OR: 3.22, 95% CI: 1.412 - 7.355), flavor preferences (OR: 18.857, 95% CI: 6.580 - 54.045), lack of parental guidance (OR: 3.273, 95% CI: 0.627 - 17.071), depression (OR: 3.692, 95% CI: 1.520 - 8.970), easy accessibility (OR: 24.00, 95% CI: 5.253 - 109.650), bad company (OR: 3.431, 95% CI: 1.461 - 8.057) and cultural influences (OR: 9.333, 95% CI: 1.994 - 43.681), However in multivariate analysis while controlling all other risk factors, fashion / social influence (OR: 59.030, CI: 10.390 - 335.363), flavor preferences (OR: 4.386, CI: 0.866 - 22.214) lack of parental guidance (OR: 13.031, CI: 0.756 - 224.518) and easy accessibility (OR: 18.579, CI: 1.742 - 198.118) were found significantly associated with shisha smoking in males. Conclusion: Shisha smoking in males was found significantly associated with fasion / social influence, flavor preferences, lack of parental guidance and easy accessibility.