The role of thermal cycling of inverted P3HT:PCBM-based polymer solar cells is reported. We found that thermal cycling between -40 °C and 85 °C up to 200 cycles had no significant effect on solar cell efficiency and mechanical integrity. On the contrary, the solar cells exhibited a slight increase in fracture resistance, similar to that reported for a post-electrode deposition thermal annealing at 85 °C. Gc increased from 2.6 J/m2 for our control solar cells to a sustained maximum value of 4.0 J/m2 after 25 thermal cycles. Surface analysis on the fractured samples revealed the formation of an intermixed layer between P3HT:PCBM and PEDOT:PSS, causing the debond path to change from adhesive between P3HT:PCBM and PEDOT:PSS to meandering through the intermixed layer. A kinetic analysis was used to model the effect of thermal cycling on the Gc values of polymer cells. The model revealed for cycling between -40 °C and 85 °C that 25 cycles are needed to reach the maximum Gc, which is consistent with our experimental results. After 5 thermal cycles, the effects of heating and cooling have little impact on the mechanical stability of polymer solar cells.