Genetic polymorphisms of platelet endothelial cell adhesion molecule-1 (PECAM-1) were found to play roles in atherosclerotic events. We determined PECAM-1 polymorphisms, soluble PECAM-1, and CD40L levels in rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) and evaluated their associations with clinical atherosclerotic complications. We included 100 RA patients, 81 SLE patients, and 94 healthy controls. The clinical features about the patients were obtained from medical records. Past cardiovascular complications were recorded. The most frequent gene polymorphisms of PECAM-1 were studied in our genetics laboratory. Soluble PECAM-1 and CD40L levels in serum were determined with ELISA. The frequencies of 373C (rs668) and 1688A (rs12953) alleles were higher in RA patients when compared to controls (p values, 0.028 and 0.016). RA and SLE patients had significantly higher allele frequencies for 2008A (rs1131012) when compared to controls (p values, 0.016 and 0.001). SLE patients had significantly more frequent AA genotype for rs1131012 polymorphism than RA patients and controls (p values, 0.007 and <0.001). Soluble PECAM-1 level was significantly higher in RA patients than in SLE patients and healthy controls (p values <0.001). Atherosclerotic complications were more frequent in SLE patients with AG genotype (rs12953) than those with AA genotype (p = 0.021). SLE patients with CC genotype (rs668) had a significantly lower frequency of atherosclerotic complications than those with CG genotype (p = 0.045). Nevertheless, in multivariate analysis, there was no association between genotype and atherosclerotic complications. We found associations between various PECAM-1 polymorphisms in RA and SLE; PECAM-1 and soluble CD40 ligand (sCD40L) levels were significantly higher in RA patients than in SLE and control groups. PECAM-1 polymorphisms in SLE were protective against atherosclerotic complications.