Background: Effective strategies to combat childhood obesity are challenging, especially among South Asian girls. We conducted a pilot cluster trial of a school-based physical activity programme among preadolescent girls to determine the feasibility (recruitment, retention and implementation) of the programme and influence on blood pressure (BP) and body mass index (BMI). Methods: This two-arm parallel cluster intervention trial was conducted in four similar all-girls public sector schools in Karachi over a 20-week period. All girls aged 9-11 years were included. Intervention was a physical activity programme of 30 min duration four times a week. Primary outcome was to assess the feasibility of the physical activity programme defined as recruitment and retention >70% and treatment fidelity of >80% of physical activity programme. Secondary outcomes were changes in systolic BP (SBP), diastolic BP (DBP) and BMI from baseline to follow-up. Results: A total of 360 participants were invited to participate, 280 girls met eligibility criteria, and were recruited; 131 (77%) in the intervention group and 146 (87%) in control group. At follow-up, the overall retention of participants was 222 (79.2%); 105 (80.1%) in the intervention group and 117 (78.5%) in the control group. The difference in mean change from baseline to follow-up in SBP, DBP and BMI score was 1.9 mm Hg, 0.7 mm Hg and 0.55 kg/m2 between intervention and control arms, respectively. Conclusions: A school-based physical activity programme in a public sector girls school of urban Pakistan is feasible. There was a favourable trend in BP and BMI at follow-up. (Clinical trial ID NCT 00533819).