Background: Semi-permanent fillers are among the most favorable fillers on the market. Through their unique mode of action and its associated lasting aesthetic effect, they take an exceptional position. Objective: To compare the two semi-permanent fillers Poly-L-Lactic Acid (PLLA) and calcium hydroxylapatite (CaHA) in reference to the aesthetic result, patient satisfaction and side effects. Methods: Studies on side effects, patient satisfaction and aesthetic results after augmentation with semi-permanent fillers were analyzed. Results: Semi-permanent fillers seem excellently suited for the augmentation of very deep wrinkles particularly in the lower half of the face. In general, high patient satisfaction can be determined with both fillers. Here, the effect from the polylactic acid can be verified for up to two years while no effect could be verified already after one year in a majority of the patients augmented with CaHA. Short-term side effects such as bleedings or erythema in the region of the augmented area have been observed in both fillers during augmentation. The incidence of nodules and granulomas seems significantly higher in augmentations with PLLA compared to CaHA. Rare side effects such as an embolization of a blood vessel caused by the implant have been described for both fillers in case reports. Conclusion: Semi-permanent fillers are superbly suited for wrinkle augmentation. Which filler is the preferred one in what case depends strongly on the individual needs of the patient and the therapist’s experience.