Enrollment in ALS trials has not been systematically studied. We surveyed the ALS Research Group (ALSRG) to learn their impressions of enrollment at ALS clinics across North America. We also reviewed completed ALS trials to determine an enrollment rate (subjects per site per month), its variability across trials, whether it is changing over time, and whether it is influenced by 'trial factors'. ALSRG members were polled via an online survey. ALS trials were identified by literature review and investigator contact. Enrollment rate versus publication year was plotted for each trial. Models were created to examine how 'trial factors' were associated with enrollment rate. By survey, percent enrollment is 25% and highly variable (range 0-75%). By literature review, enrollment rate is 2.2 participants/site/month and highly variable (range 0.1-7.5). Enrollment is not improving over time; no 'trial factor' explains the variability in enrollment across trials. Behaviors among clinic directors and patients were identified that may influence enrollment. In conclusion, ALS trial enrollment rate is low, highly variable and not influenced by trial design factors. 'Patient factors' and 'physician factors' may play more important roles in influencing enrollment, as in oncology trials. Our survey data support this idea, and provide potential mechanisms for improving enrollment.