Current analysis of unicondylar knee replacements (UKRs) by national registries is based on the pooled results of medial and lateral implants. Consequently, little is known about the differential performance of medial and lateral replacements and the influence of each implant type within these pooled analyses. Using data from the National Joint Registry for England and Wales (NJR) we aimed to determine the proportion of UKRs implanted on the lateral side of the knee, and their survival and reason for failure compared with medial UKRs. By combining information on the side of operation with component details held on the NJR, we were able to determine implant laterality (medial versus lateral) for 32 847 of the 35 624 unicondylar replacements (92%) registered before December 2010. Of these, 2052 (6%) were inserted on the lateral side of the knee. The rates of survival at five years were 93.1% (95% confidence interval (CI) 92.7 to 93.5) for medial and 93.0% (95% CI 91.1 to 94.9) for lateral UKRs (p = 0.49). The rates of failure remained equivalent after adjusting for patient age, gender, American Society of Anesthesiologists (ASA) grade, indication for surgery and implant design using Cox’s proportional hazards method (hazard ratio for lateral relative to medial replacement = 0.88 (95% CI 0.69 to 1.13); p = 0.32). Aseptic loosening/lysis and unexplained pain were the main reasons for revision in both groups, although the reasons did vary depending on whether a mobile- or a fixed-bearing design was used. At a maximum of eight years the mid-term survival rates of medial and lateral UKRs are similar.