Abstract Introduction. For anticancer drug development, it is crucial that patients participate in early-phase clinical trials. The main aim of this study was to gain insight into the motivations and other variables influencing patients in their decision to participate in phase I oncology trials. Materials and Methods. Over a period of 25 months, all patients who were informed about (specific) phase I trials in our cancer center were retrospectively included in this study. Data on providing informed consent and final phase I enrollment were collected. Results. In total, 365 patients, with a median age of 59 years and a median World Health Organization performance status score of 1, were evaluated. The majority of patients (71%) were pretreated with systemic therapy, with a median of two lines. After specific study information had been given, 145 patients (40%) declined informed consent, 54% of them mainly because of low expectations regarding treatment benefits and concerns about potential side effects. Patients who had received previous systemic therapy consented more frequently than others. After initial consent, 61 patients (17%) still did not receive study treatment, mostly because of secondary withdrawal of consent or rapid clinical deterioration prior to first dosing. Discussion. After specific referral to our hospital for participation in early clinical trials, only 44% of all patients who were informed about a specific phase I trial eventually participated. Reasons for both participation and nonparticipation were diverse. Patient participation rates could be improved by forming an experienced and dedicated study team.