Background-Phase I studies in cancer have changed in recent years. With the advent of new less toxic targeted agents, more patients may now be candidates for new drug studies earlier in the course of their disease. It is to the advantage of the members of the oncology community to know more about the details and requirements for participation in early phase clinical trials so they can advocate for their patients and help them decide when such trials may be an appropriate choice. In order to examine the work intensity of early phase cancer clinical trials, we compared the study requirements of phase I and II protocols. Methods-As a surrogate of study complexity, we examined five parameters-number of physical exams, vital sign determinations, electrocardiograms (ECGs), non-pharmacokinetic laboratory tests, and pharmacokinetic (PK) sampling-in the first four weeks of protocol, in 90 studies (49 phase I and 41 phase II). Findings-From July 2004 through March 2007, there were 49 phase I trials in the Phase I Program, nine phase II studies conducted by physicians appointed in that program, and 32 phase II trials with accessible data in the Department of Thoracic/Head & Neck Medical Oncology. In the phase I versus phase II trials, there were significantly more (p < 0.05) physical exams (mean ± SE = 3.16 ± 0.24 vs. 2.22 ± 0.13), vital signs (5.63 ± 0.61 vs. 2.80 ± 0.26), ECGs (4.36 ± 1.16 vs. 0.80 ± 0.17), non-PK lab tests (18.08 ± 1.31 vs. 10.12 ± 0.65), and PKs (15.14 ± 1.79 vs 1.02 ± 0.53). These values were also significantly different (p<0.005 for each) when comparing medians by non-parametric tests. Interpretation-While both phase I and phase II trials have substantial study requirements, those for the phase I studies were significantly higher. Successful conduct of early phase clinical trials requires significant research infrastructure.