The present research was an endeavor to examine and compare the effects of digitally self-regulated and guided discovery learning instructions on Iranian EFL learners’ vocabulary acquisition. To this end, by conducting the Oxford Placement Test, 60 out of 140 Iranian EFL male and female learners from three language institutes in Isfahan, Iran, were randomly selected, and divided into three equal groups (i.e. two experimental groups and one control group). Prior to the instructions, a vocabulary pretest, designed and validated by the researchers, was conducted. Then, the experimental groups received two types of instruction, separately. The first experimental group was taught via digitally self-regulated learning (SRL) instruction based on Santangelo, Harris, and Graham’s (2008) six-stage model. The second experimental group was instructed via guided discovery learning instruction based on Brown and Campione’s (2011) stages. In contrast, the control group received the traditional method of teaching vocabulary such as word lists, dictionary use, and word translation. After conducting eight-session instructions, a posttest was administered. The data were analyzed via ANOVAs and post hoc analysis using the Tukey test. The findings of the study revealed that both digitally self-regulated and guided discovery promoted Iranian EFL learners’ vocabulary acquisition. Additionally, the findings indicated that digitally self-regulated instruction was more effective than guided discovery instruction regarding vocabulary acquisition. Eventually, the theoretical and pedagogical implications regarding language learners, teachers, and curriculum designs are also provided.