Background: Blood group of an individual is commonly determined by ABO & Rh status. The objectives of the study were to determine the frequency of ABO, Rh and ABO-Rh blood groups in students of Gomal Medical College, D.I.Khan, Pakistan. Materials & Methods: This cross-sectional study was conducted in the Department of Community Medicine, Gomal Medical College, D.I.Khan, Pakistan from April 1 to May 23, 2019. The population being accessible was taken as sample. Sample size was 452. Our research variables (attributes) were ABO (A, B, AB, O), Rh (positive and negative) and ABO-Rh (A+, B+, AB+ O+, A-, B-, AB-, O-) respectively. All variables being nominal were described by count and percentage. The estimated parameters were given as confidence interval for proportion at 95% confidence level. The observed frequency of ABO, Rh and ABO-Rh blood groups was tested against their expected frequency using chi-square goodness of fit test. Results: Out of 452 students, the frequency of ABO blood group was; A 127 (28.12%), B 165 (36.53%), AB 57 (12.62%) & O 103 (22.73%); Rh blood group was; Rh+ 408 (90.33%) & Rh- 44 (9.67%) and ABO-Rh was; A+ 116 (25.60%), B+ 148 (32.05%), AB+ 50 (11.30%), O+ 91 (20.10%), A- 11 (2.40%), B- 17 (03.70%), AB- 7 (1.50%) & O- 12 (2.60%). The observed frequency of ABO & ABO-Rh blood groups was significantly different whereas of Rh blood group was similar to expected prevalence. Conclusion: In our population, most common blood group was B+ and the least common was AB-. The observed frequency of ABO & ABO-Rh blood groups was different while of Rh was same as expected. Awareness of blood groups in populations will help in the effective management of blood banks record in routine as well as during blood related life emergency situations.