OBJECTIVE: The objective was to identify the reported factors leading to the premature termination of randomized controlled trials (RCTs). METHODS: A clinical trial registry (clinicaltrials.gov) was searched on December 15, 2008 for identification of RCTs with recruitment status “terminated”. The RCTs submitted to the registry on or after January 1, 2004 were analyzed. Submission details were reviewed to identify the reason for premature termination along with other study details. Reasons for termination were categorized according to the pre-specified categories. Descriptive statistics were used where appropriate. RESULTS: A total of 1162 RCTs that met inclusion criteria were analyzed. Reason for premature termination of trial was reported in 656 (56.45%) trials. The most frequent reasons cited for the premature trial termination were: recruitment issues (244 trials), action based on interim analysis (68 trials), sponsor's decision (63 trials), efficacy related issues (44 trials) and safety concern (39 trials). These together were responsible for premature termination of about 70% trials. Results of terminated trials were made available on the registry for only 144 (12.39%) trials. Sponsor's decision was reported as responsible for the termination of twice as many trials during phase III or IV compared to the earlier phase of development (13.5% vs. 6.5%). Out of the 78 large trials (estimated enrolment >500) reporting termination reasons, sponsor's decision (24.4%) was the most frequent reason followed by action based on interim analysis (20.5%) and efficacy and safety related issues (11.5% each). CONCLUSION: Reporting of reasons for premature termination of RCTs was low with very few reporting the results on the registry. Slow recruitment and results of interim analysis were the major factors contributing to premature termination of RCTs, where reasons were reported.