Despite efforts within the industry to finish trials on time, as many of 45% of clinical trials are completed late and approximately 80% of trials fail to meet their initial enrollment targets on time. Successful study start-up is an essential first step, and relies on overcoming a range of factors. These include country and site selecĀ­tion, streamlining and proactive planning, and patient recruitment strategy — all of which can influence decisions and have a dramatic impact on the conduct of the entire study. This article explores a framework that integrates tools, processes, and expertise to address the challenges faced in study start up. It discusses optimally selecting countries and sites; taking the guesswork out of startup; and proactive, intelligent, patient recruitment strategies.