The purpose was to report clinical experience of a video-guided spirometry system in applying deep inhalation breath-hold (DIBH) radiotherapy for left-sided breast cancer, and to study the systematic and random uncertainties, intra- and interfraction motion and impact on cardiac dose associated with DIBH. The data from 28 left-sided breast cancer patients treated with spirometer-guided DIBH radiation were studied. Dosimetric comparisons between free-breathing (FB) and DIBH plans were performed. The distance between the heart and chest wall measured on the digitally reconstructed radiographs (DRR) and MV portal images, dDRR(DIBH) and dport(DIBH), respectively, was compared as a measure of DIBH setup uncertainty. The difference (Δd) between dDRR(DIBH) and dport(DIBH) was defined as the systematic uncertainty. The standard deviation of Δd for each patient was defined as the random uncertainty. MV cine images during radiation were acquired. Affine registrations of the cine images acquired during one fraction and multiple fractions were performed to study the intra- and interfraction motion of the chest wall. The median chest wall motion was used as the metric for intra- and interfraction analysis. Breast motions in superior-inferior (SI) direction and "AP" (defined on the DRR or MV portal image as the direction perpendicular to the SI direction) are reported. Systematic and random uncertainties of 3.8 mm and 2mm, respectively, were found for this spirometer-guided DIBH treatment. MV cine analysis showed that intrafraction chest wall motions during DIBH were 0.3mm in "AP" and 0.6 mm in SI. The interfraction chest wall motions were 3.6 mm in "AP" and 3.4 mm in SI. Utilization of DIBH with this spirometry system led to a statistically significant reduction of cardiac dose relative to FB treatment. The DIBH using video-guided spirometry provided reproducible cardiac sparing with minimal intra- and interfraction chest wall motion, and thus is a valuable adjunct to modern breast treatment techniques.