Protocol deviations are common challenges in randomized controlled trials (RCTs) and can influence the validity, reliability, and interpretation of study findings. This chapter defines protocol deviation and outlines key analytical approaches to address such deviations, including intention-to-treat (ITT) analysis, which preserves randomization by analyzing participants as originally assigned; per-protocol analysis, which includes only those who adhered strictly to the study protocol; and as-treated analysis, which categorizes participants according to the treatment actually received. The strengths, limitations, and appropriate applications of each method are discussed to guide researchers in selecting the most suitable strategy for maintaining the integrity of RCT conclusions.