The objective of this study was to determine the effects of caffeine ingestion and CYP1A2 polymorphism on Bax and Bcl-2 levels, as apoptosis markers, in acute resistance exercise (RE). In a randomized, double-blind, placebo-controlled, crossover study, 15 trained men completed acute RE at 85% of 1RM. The subjects ingested either caffeine (CAF, 6 mg.kg−1 body mass) or placebo (PLA) 1 h prior to the exercise. Blood samples were taken pre-exercise (PRE), immediately post (POST), and 15 min (15 min-POST) post RE for measuring the serum concentrations of Bax and Bcl-2 biomarkers. The CYP1A2 -163C>A polymorphisms were analyzed by amplification refractory mutation system–polymerase chain reaction (ARMS–PCR) in genomic DNA samples which were isolated from the whole blood samples. The subjects were classified as either AA (n= 8) or AC/CC genotypes (n=7). At POST, Bax concentrations were significantly higher in PLA AC than PRE (p=0.014), CAF AA (p=0.003), CAF AC/CC (p=0.039), and PLA AA (p=0.034). No significant changes were observed in Bcl-2 levels at POST compared to PRE in both groups of CAF or PLA (p>0.05). However, Bcl-2 levels in 15 min POST were significantly higher in CAF AA than in CAF AC/CC (p=0.003). Changes in the percentage of Bax/Bcl-2 ratio were significantly higher in PLA AC/CC at POST when compared with CAF AA (p=0.002) or CAF AC/CC (p=0.007), and were significantly lower in CAF AA at 15min POST than in PLA AA (p=0.039). The findings suggested that exercise alone could accelerate apoptosis in the AC/ CC group, while caffeine appears to attenuate susceptibility of cells to apoptosis.