The purpose of the current study was to predict intraocular pressure (IOP) using color fundus photography with a deep learning (DL) model, or, systemic variables with a multivariate linear regression model (MLM), along with least absolute shrinkage and selection operator regression (LASSO), support vector machine (SVM), and Random Forest: (RF). Training dataset included 3883 examinations from 3883 eyes of 1945 subjects and testing dataset 289 examinations from 289 eyes from 146 subjects. With the training dataset, MLM was constructed to predict IOP using 35 systemic variables and 25 blood measurements. A DL model was developed to predict IOP from color fundus photographs. The prediction accuracy of each model was evaluated through the absolute error and the marginal R-squared (mR2), using the testing dataset. The mean absolute error with MLM was 2.29 mmHg, which was significantly smaller than that with DL (2.70 dB). The mR2 with MLM was 0.15, whereas that with DL was 0.0066. The mean absolute error (between 2.24 and 2.30 mmHg) and mR2 (between 0.11 and 0.15) with LASSO, SVM and RF were similar to or poorer than MLM. A DL model to predict IOP using color fundus photography proved far less accurate than MLM using systemic variables.