Background: Adolescents are at substantial risk of acquiring behaviors which might influence their health status. This study was aimed to assess the proportion of school going adolescents (both males and females) with poor self-perceived health and its associated factors. Methodology: A cross-sectional study was conducted in three major cities of Pakistan i.e. Karachi, Lahore and Quetta. From each city, six (6) secondary schools were randomly selected (3 public and 3 private). Pre-tested, self-administered questionnaire was distributed to students. Binary logistic regression analysis was conducted to determine independent factors associated with poor self-perceived health. Results: Approximately 29% adolescents (119/414) reported poor self-perceived health. Individual and parental factors significantly associated with poor self-perceived health were being male (AOR = 1.75, 95% CI: 1.09 – 2.79), living in extended family (AOR = 2.65, 95%CI: 1.66 – 4.22), unskilled employment of father (AOR = 2.17, 95% CI: 1.35 – 3.48), lack of parental-child communication (AOR = 1.74, 95% CI: 1.03 – 2.91) and unfair treatment by parents (AOR = 1.80, 95% CI: 1.09 – 2.96). Life style factors such as use of smokeless tobacco (AOR = 2.14, 95% CI: 1.26 – 3.96) and unhealthy diet (AOR = 3.60, 95% CI: 1.76 – 7.33) were associated with poor self-perceived health. Conclusion: Better employment opportunities for father, parental counseling and increase awareness for adolescents about healthy diet are recommended to improve adolescent self-perceived health in Pakistan.