Purpose: The accuracy of analytical dose calculations (ADC) and dose uncertainties resulting from anatomical changes are both limiting factors in proton therapy. For the latter, rapid plan adaption is necessary, whereas for the former, Monte Carlo (MC) approaches are instead being increasingly recommended. These however are inherently slower than analytical approaches, potentially limiting the ability to rapidly adapt plans. Here, we compare the clinical relevance of uncertainties resulting from both. Materials and Methods:Five non-small-cell lung cancer (NSCLC) patients with up to nine CTs acquired during treatment and five paranasal (HN) patients with 10 simulated anatomical changes (sinus filling), were analyzed. On the initial planning-CTs, treatment plans were optimized and calculated using an ADC and then recalculated with MC. Additionally, all plans were recalculated (non-adapted) and re-optimized (adapted), on each repeated CT using the same ADC as for the initial plan and resulting dose distributions compared.Results: When comparing analytical and MC calculations in the initial treatment plan and averaged over all patients, 94.2% (NSCLC) and 98.5% (HN) of voxels had differences <±5% and only minor differences in CTV V95 (average <2%) were observed. In contrast, when re-calculating nominal plans on the repeat (anatomically changed) CTs, CTV V95 degraded by up to 34%. Plan adaption however restored CTV V95 differences between adapted and nominal plans to <0.5%. Adapted OAR doses remained the same or improved. Conclusion:Dose degradations caused by anatomical changes are substantially larger than uncertainties introduced by the use of analytical instead of MC dose calculations. Thus, if the use of analytical calculations can enable more rapid and efficient plan adaption than MC approaches, they can, and indeed should be used for plan adaption for these patient groups.