Background: The association between peroxisome proliferators-activated receptor gamma (PPAR gamma) Pro12Ala polymorphism and colorectal cancer (CRC) risk is still controversial. A meta-analysis was performed. Material/Methods: We conducted a literature search using PubMed, EMBASE, and Cochran databases. The pooled odds ratio (OR) with 95% confidence intervals (CIs) were calculated. Fixed-effects and random-effects models were used. Dominant model, recessive model, and additive model were used in this meta-analysis. Results: Fifteen studies including 13575 cases and 17085 controls were included in our meta-analysis. Result of this meta-analysis found that PPAR gamma Pro12Ala polymorphism was significantly associated with a reduced risk of CRC (OR=0.90; 95% CI 0.83-0.98; P=0.01). No significant association was found between PPAR gamma Pro12Ala polymorphism and CRC risk in Asians (OR=0.80; 95% CI 0.60-1.09; P=0.15). However, PPAR gamma Pro12Ala polymorphism was significantly associated with a reduced risk of CRC in Caucasians (OR=0.91; 95% CI 0.83-0.99; P=0.03). When stratified analysis was performed by CRC site, no positive association was found between PPAR gamma Pro12Ala polymorphism and rectal cancer (OR=0.95; 95% CI 0.74-1.22; P=0.71). However, a reduced risk of colon cancer was observed (OR=0.85; 95% CI 0.76-0.94; P=0.002). Conclusions: In summary, this study suggests that PPAR gamma Pro12Ala polymorphism was a protective factor of CRC.