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A genetic association of knee osteoarthritis (OA) and a C/T transition single nucleotide polymorphism (SNP) (rs912428) located in intron 1 of the LRCH1 gene has recently been reported in European Caucasians; however, the results are inconsistent. Our objective was to evaluate the association in different knee OA populations. Three case-control association studies were conducted in Han Chinese, Japanese, and Greek Caucasian populations. The LRCH1 SNP was genotyped in patients who had primary symptomatic knee OA with radiographic confirmation and in matched controls, and the association was examined. We performed a meta-analysis for the studies together with results of two previous papers using the DerSimonian-Laird procedure and calculated the power of the pooled studies by the software R. A total of 1,145 OA patients and 1,266 controls were genotyped. No significant difference was detected in genotype or allele frequencies between knee OA and control groups in the three populations (all P > 0.05). Association was not observed even after stratification by gender and Kellgren/Lawrence (K/L) scores. Meta-analysis also supported the lack of association between LRCH1 and knee OA. The strong heterogeneity between original and replication studies was detected in Caucasian populations. However, a tendency for the increase of TT genotype was observed in the European populations (OR = 1.46, P = 0.06). The powers for European and Asian replication studies were less than 0.8. Our results suggest that there is no association between LRCH1 and knee OA. However, lack of association should be concluded by further replication studies.