Context The demand for higher education is one of the main issues, which should be considered by managers and planners considering the reduced academic population. Currently, distance education institutions are among the most important centers of higher education according to their special mission. The main objective of this study was to identify the determinant economic factors in students’ enrollment in open and distance universities. Methods This study utilized the documentary - analytical method, time series, and ordinary least square regression model. In this study, the sample size consisted of 500 Payam-E-Noor University (PNU) centers. The sample included the number of applicants of BA of the academic years 2001 to 2014 in PNU and the reliability of independent variables was confirmed using the Dickey Fuller Test. Effective variables for distance education were first derived using the Delphi method. In the Delphi method, the indices and variables were first extracted by examining the documents, distributed to 15 professors of higher education, economic sciences, and social sciences, and finally, the indicators were approved. Results This study showed that the earning per master’s degree was 0.144 (P = 0.043); student scholarship and loan (0.583, P = 0.035) were significantly higher and had positive effects on the numbers of PNU applicants compared to other variables. Diploma degree income (-0.083, P = 0.038) and gross domestic production (-22.10, P = 0.092) had significantly higher and negative effects on students’ entrance to PNU. Conclusions Expecting future income and students’ scholarships and loans had a determinant impact on the entry of students in PNU. Therefore, educational planners in this university should pay attention to these points.