OBJECTIVE: To systematically review the literature related to the effectiveness of parents' active involvement during painful interventions for their preterm infants. DATA SOURCES: We performed a systematic search of PubMed, EMBASE/Ovid, CINAHL, Livivio, and PsycInfo using the keywords "preterm infants," "pain," and "parents." STUDY SELECTION: Articles were eligible for inclusion if they were published between 2000 and 2021 and reported randomized controlled trials (RCTs) in which preterm infants underwent painful interventions, and parents were present and actively involved in pain-reducing measures. DATA EXTRACTION: We used the Consolidated Standards of Reporting Trials (CONSORT) checklist for RCTs for data extraction. We assessed methodologic quality using critical appraisal for RCTs according to the Joanna Briggs Institute. DATA SYNTHESIS: In total, 22 articles met the inclusion criteria. These articles reported 18 studies focused on kangaroo/skin-to-skin care, one focused on breastfeeding, and two focused on facilitated tucking. The methods used to evaluate pain in the infant varied substantially. Overall, kangaroo/skin-to-skin care and facilitated tucking resulted in clinically and statistically significant decreases in pain. For breastfeeding, effectiveness was linked to a more mature sucking pattern of the preterm infant. CONCLUSION: The current evidence suggests that involving parents in pain-reducing measures during painful interventions for their preterm infants is beneficial. However, more research is needed for the different methods of involving parents in pain-reducing measures.