Objective To evaluate the effect of problem-based learning(PBL) and case-based leaning(CBL) during clerkship rotation of ophthalmology with Kirkpatrick's Model. Methods Totally 120 five-year program students enrolled in 2016 and received clinical training from April to June 2019 at Ophthalmology Department of Third Affiliated Hospital of Guangzhou Medical University were enrolled in this research program. The students were randomized into groups of PBL and CBL with 60 in each. The effect of two teaching methods was evaluated by Kirkpatrick's four-level model. The Chi-square test or the t test was used to analyze the data. Results The students of two groups were all satisfied with the scores more than 4 points. The satisfaction scores of students from PBL group and from CBL group were (4.23±0.54) and (4.45±0.49) respectively with stimulating learning interest and students showed preference to CBL method, the score of satisfaction with building of working confidence from CBL group (4.50 ± 0.24) was significantly higher than that from PBL group(4.36±0.32) (all P<0.05). In the view point of learning outcomes, the average theoretical assessment scores of PBL and CBL groups were (85.59±6.63) and (83.98±9.72) respectively without significant difference(P=0.291). At the behavior level there was a high consistency between the results of self-assessment and faculty-assessment of the two groups. PBL method is believed to be more conducive to the cultivation of students' capacity building of to self-oriented learning[(8.88±1.92) vs.(8.02±2.69), (8.48±1.92) vs. (7.60±2.62)], literature reading [(8.82±3.17) vs. (7.58±3.33), (8.41±2.39) vs. (7.44±2.30)] and research thinking [(8.36±3.09) vs. (7.21±2.29), (8.11±2.71) vs. (7.01±2.10)]. CBL method is more conducive to the capacity building of students in patient assessment [(7.45±3.18) vs. (8.72±2.26), (7.04±2.16) vs. (8.42±2.71)] and standardized regulation of clinical operation [(7.20±3.29) vs. (8.32±2.44), (7.07±2.20) vs. (8.16±2.66)](all P<0.05). In terms of occupation intendment, four students from PBL group and five students from CBL group are interested in becoming an ophthalmologist, and already prepared to register for entrance examination of ophthalmology graduate program(P=0.729). Conclusions By using Kirkpatrick's Model, we found that PBL method is more conducive to improving students' capacity building for self-oriented learning and scientific research, while CBL method is more conducive to support the development of students' clinical reasoning and to stimulate their learning interest as well as to constitute their working confidence.