Caveolin-3 (Cav-3) is a critical scaffolding protein essential for caveolae formation. In cardiomyocytes, caveolae serve as important Ca2+ microdomains where several ion channels localize including voltage-gated Na+ and L-type Ca2+ channels (LTTCs). Our previous studies have shown that Long QT Syndrome (LQTS)-associated Cav-3 F97C and S141R mutations increased sodium channel late current, but it is unknown if these mutations impact LTTCs. We co-expressed Cav-3 WT, F97C, or S141R with Cav1.2 + Cavβ2cN4 in HEK 293 cells and measured LTCC currents (ICa,L) using whole-cell perforated patch clamp with 10 mM Ca2+ or 10 mM Ba2+ as the charge carrier. Cav-3 S141R transfected cells showed increased ICa,L peak current density (−13.95±1.86 pA/pF, p<0.05) compared to F97C (−7.59±1.99 pA/pF) and WT (−9.47±2.38 pA/pF). Analysis of ICa,L inactivation shows that Cav-3 F97C (r100: 0.35±0.03) slows inactivation compared to S141R and WT (0.24±0.04 and 0.13±0.03, respectively; p<0.05). However, there were no significant differences in IBa,L current density or inactivation observed between Cav-3 WT, F97C, and S141R. Experiments were also performed in mouse neonatal ventricular myocytes transfected with Cav-3 WT, F97C, or S141R. Cav-3 S141R (−6.98±0.97 pA/pF) increased peak ICa,L current density compared to F97C and WT (−2.62±0.87 and −3.76±0.72 pA/pF, respectively; p<0.05). Analysis of ICa,L inactivation showed that both Cav-F97C and S141R (r75: 0.13±0.02 and 0.13±0.02, respectively, p<0.05) slowed inactivation compared to WT (0.05±0.02). LQT Cav-3 F97C and S141R mutations alter calcium-dependent LTTC function by reducing Ca-dependent inactivation and for S141R increasing current density. In conclusion, these results suggest a newly identified role in which Cav-3 is part of the complex which regulates calcium-dependent inactivation of cardiac LTTCs. Furthermore, the LQT Cav-3 mutations, F97C and S141R, show important gain-of-function effects which will prolong repolarization and contribute to arrhythmogenesis.