Aims: The aim of present study was to compare the knowledge and practice of staff nurses pre and post teaching about thrombolytic drug therapy. Materials and Methods: This cross sectional, observational study consisted of consenting subjects attending Out Patients department for routine antenatal checkup. Data was collected with all subjects in respect to socio demographic information and structured knowledge questionnaire, observational checklist and opinionnaire was applied. Results: Sample size of staff nurses were 30 with 93.3% of females and professional qualification of G.N.M. were included for the study. 53.3% of the staff nurses had 2–6 yrs of experience and 70% had administered thrombolytic drug therapy in past. The overall pre–test knowledge mean score was 25.8% whereas in post test knowledge mean score was 38.33%. Conclusions: This study finds a significant improvement in knowledge and practice of thrombolytic drug therapy by staff nurses following teaching and training program.