The objectives of the study was to compare the effectiveness of online classes versus offline classes on knowledge and practice regarding IV cannulation among undergraduate students. Ninety-eight undergraduate students were selected using purposive sampling technique. Pre-test level of knowledge was assessed by using self-structured questionaries and level of practice was assessed by using OSCE checklist for both online and offline groups. Following the pre-test, through zoom online class taken with power point presentation regarding IV cannulation and video on IV cannulation procedure was displayed to the students. For offline group student’s investigator taken class by using power point presentation on IV cannulation and demonstration of IV cannulation was carried out by the investigator with the help of IV hand mannequin in the fundamental lab. The analysis reveals that, regarding knowledge on IV Cannulation the online post-test mean scores (16.55) and the offline post-test mean scores (17.08) . This shows that there is no significant difference between the means post-test knowledge scores of online and offline group at p not lesser than 0.05 level, Regarding practice on IV Cannulation the offline post-test mean scores (18.06) has increased from the online post-test mean scores (16.27) . This shows that the mean difference between offline and online post-test level of practice on IV Cannulation, which was significantly difference at p ˂ 0.01 level. Therefore, we can conclude that the offline classes are effective in improving practice of the students than the online classes.